TUMOUR MARKERS

2. TUMOUR MARKERSTUMOUR MARKERS
PRESENTED by---Dr.JYOTINDRA SINGHPRESENTED by---Dr.JYOTINDRA SINGH
MODERATOR–MODERATOR– Dr. A. BHASKARANDr. A. BHASKARAN

3. SEMINAR PLANSEMINAR PLAN
 INTRODUCTIONINTRODUCTION
 HISTORICAL ASPECTHISTORICAL ASPECT
 CLASSIFICATIONCLASSIFICATION
 CLINICAL APPLICATIONCLINICAL APPLICATION
 IMPORTANT MARKERSIMPORTANT MARKERS
 STAINSSTAINS
 CASE REVIEWCASE REVIEW
 RECENT ADVANCESRECENT ADVANCES
 REFERENCESREFERENCES
 TAKE HOME MESSAGETAKE HOME MESSAGE

4. Introduction
*Patient after treatment invariably asks the
clinician, “Can I be cured ?”. He might have been
cured, provided that
Pt. does not harbor micro-metastastic disease and
has no microscopic residual disease at the end of
treatment.

5. * But this question is difficult to answer,
since it is difficult to know these facts by
morphological investigations or scans
we need molecular markers which are
sensitive

7. What Are Tumor Markers?What Are Tumor Markers?
‘‘Tumor markers are metabolic products produced byTumor markers are metabolic products produced by
tumor cells or related to presence of tumor, foundtumor cells or related to presence of tumor, found
in body fluids or tissue or tumor surface of patientsin body fluids or tissue or tumor surface of patients
with cancers’with cancers’
Tumor markers are substances that can be detectedTumor markers are substances that can be detected
in higher-than-normal amounts in the blood, urine,in higher-than-normal amounts in the blood, urine,
or body tissues of some patients with certain typesor body tissues of some patients with certain types
of cancer.of cancer.
A tumor marker may be made by a tumor itself orA tumor marker may be made by a tumor itself or
by the body in response to the tumor.by the body in response to the tumor.

8. BIOLOGICAL MARKERBIOLOGICAL MARKER
 Some tumor products are appropriate to theSome tumor products are appropriate to the
tissueof origin, but others are not and aretissueof origin, but others are not and are
regarded as ectopic or inappropriate.regarded as ectopic or inappropriate.
 These products are known as “These products are known as “ biologicalbiological
markers”markers”

9. What Is An Ideal Tumor Marker?What Is An Ideal Tumor Marker?
Highly specific: low false-positive tests (inHighly specific: low false-positive tests (in
normal individuals, benign diseases)normal individuals, benign diseases)
Highly sensitive: low false-negative rateHighly sensitive: low false-negative rate
Circulating levels should correlate directly withCirculating levels should correlate directly with
the amount of viable tumor presentthe amount of viable tumor present
Sensitive and specific assays must beSensitive and specific assays must be
reproducible and widely available at areproducible and widely available at a
reasonable costreasonable cost

10. What Is An Ideal Tumor Marker?What Is An Ideal Tumor Marker?
Present in all patients with a givenPresent in all patients with a given
malignancymalignancy
Detectable in occult diseaseDetectable in occult disease
Absent in health and benign diseaseAbsent in health and benign disease
The levels should correlate with the result ofThe levels should correlate with the result of
anticancer therapyanticancer therapy
 No ideal tumor marker exists at presentNo ideal tumor marker exists at present

11. Serum Tumor MarkersSerum Tumor Markers
A help?A help?
oror
a problem?a problem?

12. Year Clinician Tumor
marker
Origin
1938 Gutman
&Gutnan
Acid
phosphatase-
enzyme
Met. Prostate
Cancer
1965 Gold &
Freedman
CEA-Fetal
antigen
GIT-cancers
1973 Kohler &
Milstein
Monoclonal
antibodies by
-Hybridoma
Tumor
antigens
Recently Yalow
&Berson
RIA-
Radioimmuno
assay
Received
Nobel prize
History of Tumor Markers
Recently developed molecular biology methods allows tumor
Markers to be characterized at the gene level.

13. ClassificationClassification
1) Tumor Markers 2) Biological markers
1) Tumor derived markers 2) Tumor associated markers
1) Tumor produced 2) Host produced

14. ClassificationClassification
Tumor derived markers Tumor associated markers
Originate from neoplastic cells
themselves
a)Steriods-which are appropriate
factors from adrenocortical tumors
b)ACTH, HCG, CEA, Calcitonin--
which are in-appropriate factors
c) Those arise from tumor stroma
eg. Hypercalcemia factors from
Breast cancers
a) Includes various, plasma &
urinary factors like Enzymes and
proteins.
b) They are produced by cells
of uninvolved orgnas -- Actue
phase proteins by liver in response
to tumor elsewhere in body
c) Produced by tissue infiltration
by metastatis-Oesteolytic
bone met. release hydroxyproline
in urine

15. Types Of Tumor MarkersTypes Of Tumor Markers
Circulating tumor markers can be categorised by functionalCirculating tumor markers can be categorised by functional
and biochemical characteristics into:and biochemical characteristics into:
Tumor antigensTumor antigens
EnzymesEnzymes
HormonesHormones
OncogenesOncogenes or gene productsor gene products
MiscellaneousMiscellaneous ..

16. Type Tumor Marker Tumor Histologies
1) Tumor antigen
a) Oncofetal * Carcinoembryonic Antigen (CEA) Colorectal, Pancreas, Breast, Lung, Gastric cancers
* Alpha-fetoprotein (AFP) HCC, Germ cell tumors
b) Polyclonal antibody-
defined
* Prostate-specific Antigen Prostatic cancer
* Tissue Polypeptide Antigen (TPA) Breast, Gynecologic cancers
c) Monoclonal antibody-
defined cancer antigens
* CA 15-3 Breast cancers
* CA 19-9 Colorectal, Pancreas, Biliary, Gastric cancers
* CA 50 Colorectal, Pancreas, Gastric cancers
* CA 125 Ovarian/ Non-ovarian gynecologic tumors
2) Enzymes
*Neuron-specific Enolase (NSE) Neuroendocrine tumors (APUDomas)
Small cell lung cancers, Medullary thyroid cancers
Islet cell tumors, Carcinoids
* Prostatic Acid Phosphatase(PAP) Prostatic cancer
3) Hormones
* Beta- Human Chorionic
Gonadotropin (β-HCG)
Germ cell tumors of testis/ ovary
Gestational trophoblastic tumors
* Gastrin, Insulin Islet cell tumors
* Thyroglobulin, Calcitonin Thryoid Cancers
4) Oncogene * erb B-2 Breast, Ovarian, Gastric cancers

17. How Are Tumor Markers Used?How Are Tumor Markers Used?
Clinical applications and UsesClinical applications and Uses
1)1) ScreeningScreening
2) Early Detection of Cancer2) Early Detection of Cancer
3) Diagnosing Cancer3) Diagnosing Cancer
4) Staging of Cancer4) Staging of Cancer
5) Determining the Prognosis for Certain Cancers5) Determining the Prognosis for Certain Cancers
6) Determining the Effectiveness of Treatment6) Determining the Effectiveness of Treatment
7) Detecting Recurrent Cancer7) Detecting Recurrent Cancer
8) To assess response to treatment8) To assess response to treatment
9) Follow up of a cancer patient9) Follow up of a cancer patient

18. 1)Screening and Early Detection of Cancer1)Screening and Early Detection of Cancer
Screening refers to testing for cancer in people who have noScreening refers to testing for cancer in people who have no
symptoms of the disease.symptoms of the disease.
Early detection refers to finding cancer at an early stage,Early detection refers to finding cancer at an early stage,
when it is less likely to have spread (and is more likely to bewhen it is less likely to have spread (and is more likely to be
treated effectively).treated effectively).
A successful screening test for the detection of cancer mustA successful screening test for the detection of cancer must
have a high sensitivity for early lesions, so as to detecthave a high sensitivity for early lesions, so as to detect
disease in asymptomatic patients with small curable tumordisease in asymptomatic patients with small curable tumor
burdensburdens..

19. The most widely accepted marker is theThe most widely accepted marker is the prostate-prostate-
specific antigen (specific antigen (PSA)PSA) blood test, which isblood test, which is
used (along with theused (along with the DREDRE digital rectal exam) todigital rectal exam) to
screen forscreen for prostateprostate cancer.cancer. ..
SerumSerum αα-fetoprotein-fetoprotein and ultrasound scanningand ultrasound scanning
are used for screening for HCC in endemic areasare used for screening for HCC in endemic areas
Screening and Early Detection of CancerScreening and Early Detection of Cancer

20. Detection methodsDetection methods
1) Detection by values from serum, urine
2) Cytology
3) Immunohistology
4) Cytogenetics
5) Immunologic detection methods
a) T-cell based
b)Antibody based
6) Genetic Analysis

21. 2)Diagnosing Cancer2)Diagnosing Cancer
Tumor markers are usually not used to diagnose cancer, butTumor markers are usually not used to diagnose cancer, but
can help determine a likely presence of cancer.can help determine a likely presence of cancer.
They can also help diagnose the source of widespreadThey can also help diagnose the source of widespread
metastases of an unknown primary.metastases of an unknown primary.
Eg: The presence of a high level of CA 125 will stronglyEg: The presence of a high level of CA 125 will strongly
suggest ovarian cancer, even if surgery can’t identify thesuggest ovarian cancer, even if surgery can’t identify the
source and treatment can then be tailored to this type ofsource and treatment can then be tailored to this type of
cancer.-Endometrial CA-nodal/metastatic diseasecancer.-Endometrial CA-nodal/metastatic disease

22. DIAGNOSING CANCERDIAGNOSING CANCER
Elevated circulating levels ofElevated circulating levels of
gastrin (gastrinomagastrin (gastrinoma),), insulin (insulinomainsulin (insulinoma),),
tryptophan/ urinary 5-HIAAtryptophan/ urinary 5-HIAA (carcinoid syndrome)(carcinoid syndrome)
form major diagnostic criteria in endocrine tumors.form major diagnostic criteria in endocrine tumors.
Serum AFP level >500ng/ml in presence of Cirrhosis isSerum AFP level >500ng/ml in presence of Cirrhosis is
diagnostic for Hepatocellular Carcinomadiagnostic for Hepatocellular Carcinoma
Raised Calcitonin is diagnostic of MTCRaised Calcitonin is diagnostic of MTC

23. 3)Staging Cancer3)Staging Cancer
AJCC TNM staging forAJCC TNM staging for testicular cancerstesticular cancers incorporates theincorporates the
serum levels of tumor markers AFP,serum levels of tumor markers AFP, ββ-HCG and LDH.-HCG and LDH.
AFP (ng/ml) β-HCG (mIU/ml) LDH
S0 not elevated not elevated not elevated
S1 < 1000 <5000 <1.5 X N
S2 1000-10,000 5000-50,000 1.5-10 X N
S3 >10,000 >50,000 >10 X N

24. Germ Cell Tumor Risk ClassificationGerm Cell Tumor Risk Classification
Seminoma Nonseminoma
Good risk Any HCG
Any LDH
Nonpulmonary visceral
metastases absent
Any primary site
AFP <1000 ng/ml
HCG <5000 mIU/ml
LDH <1.5 X upper limit of normal
Nonpulmonary visceral metastases absent
Gonadal or retroperitoneal primary site
Intermediate
risk
Any HCG
Any LDH
Nonpulmonary visceral
metastases absent
Any primary site
AFP 1000-10,000 ng/ml S2
HCG 5000-50,000 mIU/ml
LDH 1.5-10 X upper limit of normal
Nonpulmonary visceral metastases absent
Gonadal or retroperitoneal primary site
Poor risk Does not exist AFP >10,000 ng/ml S3
HCG >50,000 mIU/ml
LDH >10 X upper limit of normal
Nonpulmonary visceral metastases present (eg.,
bone, liver, brain)
Mediastinal primary site
S1

25. 4) Determining the Prognosis for Cancers4) Determining the Prognosis for Cancers
Some tumor markers help show how aggressive a particularSome tumor markers help show how aggressive a particular
cancer is, or even how well it might respond to a particular drug.cancer is, or even how well it might respond to a particular drug.
Testicular cancerTesticular cancer patients with normal serum marker levelspatients with normal serum marker levels
respond better to therapy compared to those with elevated ones.respond better to therapy compared to those with elevated ones.
Absolute serum level of tumor marker may predict outcome- inAbsolute serum level of tumor marker may predict outcome- in
colorectal cancercolorectal cancer patients, prognosis worsens with greaterpatients, prognosis worsens with greater
serum levels of CEAserum levels of CEA..
eg;eg; Her-2-neu, Ki-67 & MUC-1Her-2-neu, Ki-67 & MUC-1 in Breast cancer pt.sin Breast cancer pt.s
is asociated with poor prognosisis asociated with poor prognosis

26. Determining the Effectiveness TreatmentDetermining the Effectiveness Treatment
Less expensive meansLess expensive means to monitor patients being treated for cancerto monitor patients being treated for cancer
compared to repeat chest x-rays, computed tomography (CT) scans,compared to repeat chest x-rays, computed tomography (CT) scans,
bone scans, or other complicated tests-Eg:bone scans, or other complicated tests-Eg: CEA, ThyroglobulinCEA, Thyroglobulin
If the serum marker level in the blood shows prompt decline, theIf the serum marker level in the blood shows prompt decline, the
treatment is having good response.eg:treatment is having good response.eg: CA-125CA-125
Slow or incomplete decline in the marker level accompanySlow or incomplete decline in the marker level accompany
incomplete response.incomplete response.
eg:eg: ER, PR and Her-2-neuER, PR and Her-2-neu --overexpression inBreast cancer patients has--overexpression inBreast cancer patients has
therapeutic drug and treatment valuetherapeutic drug and treatment value

27. Detecting Recurrent CancerDetecting Recurrent Cancer
Can sometimes detect cancer recurrence before clinical orCan sometimes detect cancer recurrence before clinical or
radiological evidence of recurrence Eg: CA-125 three monthsradiological evidence of recurrence Eg: CA-125 three months
before.before.
Biochemical evidence of failure precedes clinical evidence byBiochemical evidence of failure precedes clinical evidence by
about 5 to 6 monthsabout 5 to 6 months
Eg: PSA (prostate cancer), human chorionic gonadotropinEg: PSA (prostate cancer), human chorionic gonadotropin
(HCG) (gestational trophoblastic tumors, germ cell cancers of(HCG) (gestational trophoblastic tumors, germ cell cancers of
the ovaries and testicles), CA 125 (epithelial ovarian cancer),the ovaries and testicles), CA 125 (epithelial ovarian cancer),
CA 15-3 (breast cancer), CEA (colorectal cancer)CA 15-3 (breast cancer), CEA (colorectal cancer)

28. FOLLOW UP OF
PATIENTWell differentiated Thyroid cancers: Papillary/Follicular Ca
Serum TG -Thyroglobulin
After Total Thyroidectomy and Radio-iodine ablation
Ideally it should not be recordable
value >2ng/ml
+ve for recurrence
Serum antithyroglobulin
antibodies
-ve +ve
Follow up

29. TUMOUR MARKERSTUMOUR MARKERS
AN OVERVIEWAN OVERVIEW

30. Alpha-fetoprotein (AFP)Alpha-fetoprotein (AFP)
Oncofetoprotein- glycoprotein,Oncofetoprotein- glycoprotein, normally producednormally produced
by the fetal yolk sac, fetal liver-kupffer cellsby the fetal yolk sac, fetal liver-kupffer cells
Normal serum value: < 15 ng/mlNormal serum value: < 15 ng/ml
t1/2: 4 to 6 dayst1/2: 4 to 6 days
Malignancies:Malignancies:
Hepatocellular carcinoma- Elevated in 80 % CaHepatocellular carcinoma- Elevated in 80 % Ca
Non-seminomatous germ cell tumors ofNon-seminomatous germ cell tumors of testistestis- yolk- yolk
sac/ embryonal/ mixed GCTsac/ embryonal/ mixed GCT

31. AFPAFP
OvarianOvarian
20~70%20~70% germ cell tumorsgerm cell tumors (yolk sac(yolk sac
tumors, embryonal cell carcinoma)tumors, embryonal cell carcinoma) exceptexcept
dysgerminomadysgerminoma
Gastric/ pancreatic cancer (20% cases)Gastric/ pancreatic cancer (20% cases)
Colorectal cancerColorectal cancer
Lung cancerLung cancer
CSFCSF ：： plasma ratio of AFP > 1:40 → suggest CNSplasma ratio of AFP > 1:40 → suggest CNS

32.  BenignBenign ：： conditions that cause hepaticconditions that cause hepatic
parenchymal inflammation, hepatic necrosis andparenchymal inflammation, hepatic necrosis and
hepatic regenerationhepatic regeneration
 ex.ex. hepatitishepatitis,,
 pregnancy,pregnancy,
 primary biliary cirrhosis,primary biliary cirrhosis,
 extrahepatic biliary obstructionextrahepatic biliary obstruction

33. AFPAFP
AFP is helpful inAFP is helpful in initial diagnosisinitial diagnosis,, follow-up responsefollow-up response to treatment,to treatment,
to determineto determine prognosisprognosis, to detect, to detect recurrence earlyrecurrence early
High levels (>500 ng/ml) are exclusively present in HCC & NSGCTHigh levels (>500 ng/ml) are exclusively present in HCC & NSGCT
Following effective therapy, normalization of the serum AFPFollowing effective therapy, normalization of the serum AFP
concentration over 25 to 30 days is indicative of an appropriateconcentration over 25 to 30 days is indicative of an appropriate
declinedecline
False-positive AFP valuesFalse-positive AFP values — are rare, but can occur with tumors of— are rare, but can occur with tumors of
the gastrointestinal tract, particularly from liver damage (eg, cirrhosis,the gastrointestinal tract, particularly from liver damage (eg, cirrhosis,
hepatitis, or drug or alcohol abuse)hepatitis, or drug or alcohol abuse)
Combined USG + AFP used as screening protocol in early cases ofCombined USG + AFP used as screening protocol in early cases of
HCC in high risk areasHCC in high risk areas

34. Have A Great Day…

35. Prostate-specific antigen (PSA)Prostate-specific antigen (PSA)
Glycoprotein secreted byGlycoprotein secreted by prostatic acinar & ductal cellsprostatic acinar & ductal cells
Normal value: 2.5-4 ng/mlNormal value: 2.5-4 ng/ml
t1/2: 2-3 dayst1/2: 2-3 days
Malignancies: elevated in prostate cancer.Malignancies: elevated in prostate cancer.
Benign conditions: Benign prostatic hyperplasia (BPH),Benign conditions: Benign prostatic hyperplasia (BPH),
prostatitis, prostate surgery, cystoscopyprostatitis, prostate surgery, cystoscopy

36. PSAPSA
Elevated for at least 6-8 weeks after prostate biopsyElevated for at least 6-8 weeks after prostate biopsy
PSA is the only marker used to screenPSA is the only marker used to screen for afor a
common type of cancer (although some medicalcommon type of cancer (although some medical
groups do not recommend its use) along with (andgroups do not recommend its use) along with (and
before) digital rectal exam (DRE).before) digital rectal exam (DRE).
Highly sensitive marker for prostate cancer but lessHighly sensitive marker for prostate cancer but less
specific.specific.
The PSA test is very valuable inThe PSA test is very valuable in assessment ofassessment of
response to therapyresponse to therapy and follow-up of patients withand follow-up of patients with
prostate cancer.prostate cancer.

37. PSAPSA
Blood PSA level belowBlood PSA level below 4 ng/mL4 ng/mL means cancer is unlikelymeans cancer is unlikely andand levels greaterlevels greater
thanthan 10 ng/mL10 ng/mL mean cancer is likelymean cancer is likely. The area between 4 and 10 is a gray zone-. The area between 4 and 10 is a gray zone-
prostate biopsy is recommended for a person with a level above 4 ng/mLprostate biopsy is recommended for a person with a level above 4 ng/mL
PSA level over timePSA level over time ((PSA velocityPSA velocity- normal 0.04 ng/ml/year for age 60- normal 0.04 ng/ml/year for age 60
yrs),yrs), an increase from one year to the next may mean prostate cancer is morean increase from one year to the next may mean prostate cancer is more
likely.likely.
A helpful test when a PSA value is between 4 ng/mL and 10 ng/mL is to measureA helpful test when a PSA value is between 4 ng/mL and 10 ng/mL is to measure
the free PSA (or percent-free PSA). When the freethe free PSA (or percent-free PSA). When the free PSA makes up more thanPSA makes up more than
25%25% of the total PSA, prostate cancer is unlikely. If theof the total PSA, prostate cancer is unlikely. If the free PSA is belowfree PSA is below
10%,10%, the chance of prostate cancer is much higher (about 50%).the chance of prostate cancer is much higher (about 50%).
For patients who have been treated with surgery or radiation therapy meant toFor patients who have been treated with surgery or radiation therapy meant to
cure the disease, the PSA should fall to an undetectable (or near undetectable)cure the disease, the PSA should fall to an undetectable (or near undetectable)
level- nadir.level- nadir.

38. PSAPSA
Prostatic acid phosphatase (PAP):Prostatic acid phosphatase (PAP): was used before the PSAwas used before the PSA
test was developed but is rarely used now because the PSA test istest was developed but is rarely used now because the PSA test is
much more sensitive.much more sensitive.
Prostate-specific membrane antigen (PSMA):Prostate-specific membrane antigen (PSMA):
Blood levels increase with age and with prostate cancer.Blood levels increase with age and with prostate cancer.
PSMA is a very sensitive marker, but so far it has not proven to bePSMA is a very sensitive marker, but so far it has not proven to be
better than PSA, and its use in detecting or monitoring cancer is stillbetter than PSA, and its use in detecting or monitoring cancer is still
being studied.being studied.
Its current use is limited to PSMA scan- looks for metastasesIts current use is limited to PSMA scan- looks for metastases..

39. Carcinoembryonic Antigen (CEA)Carcinoembryonic Antigen (CEA)
Glycoprotein antigenGlycoprotein antigen
Normal serum value: <2.5 ng/mL in nonsmokers;Normal serum value: <2.5 ng/mL in nonsmokers;
<5 ng/mL in smokers<5 ng/mL in smokers
t1/2: 1 to 7 days (depends on hepatic function)t1/2: 1 to 7 days (depends on hepatic function)
Elevated in malignanciesElevated in malignancies
colorectalcolorectal
breast,breast,
pancreas,pancreas,
gastric/lung cancersgastric/lung cancers

40. CEACEA
Benign conditions:Benign conditions:
Cigarette smoking (upto 19%),Cigarette smoking (upto 19%),
Peptic ulcer disease,Peptic ulcer disease,
Inflammatory bowel diseaseInflammatory bowel disease
Cirrhosis, biliary obstructionCirrhosis, biliary obstruction
CEACEA is used tois used to monitor responsemonitor response toto
treatment, to detecttreatment, to detect recurrence earlyrecurrence early

41. CEACEA
CLINICAL USES
1) Pre-operatively: values >7.5ng/ml associated with poor
prognosis
2) Post-operatively: as measure of the completeness of tumor
resection---incomplete resection or occult metastases
3) Monitoring of tumor recurrence: Rising trend will predict
recurrent disease with in 3-4 months-even if CT-scan is normal
4) Monitor of tumor regression in metastatic disease:
serial values of CEA show either regression or progression

42. CEACEA
Prognostic value:Prognostic value: Over-all survival was decreasedOver-all survival was decreased
significantly when pre-operative CEA was >5 ng/mlsignificantly when pre-operative CEA was >5 ng/ml
(except in advanced disease)(except in advanced disease)
SensitivitySensitivity increases with advancing tumor stage:increases with advancing tumor stage:
CEA values are elevated inCEA values are elevated in
50 % of patients with N+ and50 % of patients with N+ and
75 % of patients with M+.75 % of patients with M+.

43. Malignancies with Elevated Serum CEA levelsMalignancies with Elevated Serum CEA levels
Tumor % pts. with ↑ serum CEA levels
Breast
Local 0 - 2
Metastatic 41 - 71
Colorectal
Dukes’ Stage A 3 - 5
Stage B 25
Stage C 33 - 45
Stage D 65 - 90
Gastric 30
Gynecologic
Cervical 30 - 65
Endometrial 43 - 69
Ovarian 32 - 51
Vulvar 33 - 51
Lung
Non-small cell 15 - 25
Small cell 23 - 59
Pancreas
Local 50
Metastatic 87 - 100
Medullary thyroid carcinoma 80
Benign conditions
GIT disorders Peptic ulcer
Gastritis
Pancreatitis
IBD
Hepato-biliary
diseases
Cirrhosis
Hepatitis
Obstructive
jaundice
Pulmonary
diseases
Bronchitis
Emphysema
Prostatic
disease
BPH
Renal failure

44. Beta-HCGBeta-HCG
Polypeptide- placental hormonePolypeptide- placental hormone
ElevatedElevated during pregnancyduring pregnancy
Normal serum value: < 5 mIU/ml for women; < 3 mIU/ml for malesNormal serum value: < 5 mIU/ml for women; < 3 mIU/ml for males
t1/2: 18-24 hourst1/2: 18-24 hours
Malignancies:Malignancies: blood levels are elevated in patients with someblood levels are elevated in patients with some
types oftypes of testicular and ovarian cancerstesticular and ovarian cancers (germ cell tumors)(germ cell tumors)
in gestational trophoblastic disease - mainlyin gestational trophoblastic disease - mainly choriocarcinoma,choriocarcinoma,
mediastinal germ cell neoplasmsmediastinal germ cell neoplasms

45. Beta-HCGBeta-HCG
ββ-HCG is helpful in-HCG is helpful in initial diagnosis,initial diagnosis, follow-up responsefollow-up response toto
treatment, totreatment, to determine prognosisdetermine prognosis, to, to detect recurrencedetect recurrence
early.early.
ββ-HCG-HCG does not cross blood-brain barrier easilydoes not cross blood-brain barrier easily, CSF:, CSF:
Serum ratio is > 1:60; ratio less than this is suspicious ofSerum ratio is > 1:60; ratio less than this is suspicious of
cerebral metastases.cerebral metastases.
An elevated blood level of this marker will also raiseAn elevated blood level of this marker will also raise
suspicions of cancer in certain situations. For example, in asuspicions of cancer in certain situations. For example, in a
woman who continues to have a large uterus after pregnancy has ended,woman who continues to have a large uterus after pregnancy has ended,
elevation of this marker is a possible sign of a cancer- Gestationalelevation of this marker is a possible sign of a cancer- Gestational
Trophoblastic TumorsTrophoblastic Tumors..

46. Beta-2-microglobulin (B2M)Beta-2-microglobulin (B2M)
GlobulinGlobulin
Normal serum value: < 2.5Normal serum value: < 2.5 µµg/mlg/ml
Malignancies:Malignancies: elevated in multiple myeloma,elevated in multiple myeloma,
chronic lymphocytic leukemia (CLL)chronic lymphocytic leukemia (CLL)
and some lymphomasand some lymphomas
Benign conditionsBenign conditions:: renal diseaserenal disease
B2M is useful in helping to determine prognosisB2M is useful in helping to determine prognosis
Patients with higher levels of B2M usually have a poorerPatients with higher levels of B2M usually have a poorer
prognosisprognosis

47. Bladder tumor antigen (BTA)Bladder tumor antigen (BTA)
BTA is present in theBTA is present in the urineurine of many patients withof many patients with bladderbladder
cancer.cancer.
It is not widely used, but is still being studied.It is not widely used, but is still being studied.
Reported sensitivity is 50-60% for both superficial (Tis, Ta, T1)Reported sensitivity is 50-60% for both superficial (Tis, Ta, T1)
and invasive (T2-T4) tumors and specificity is 72%.and invasive (T2-T4) tumors and specificity is 72%.
It is being used along with Nuclear Matrix Protein 22 (NMP22)It is being used along with Nuclear Matrix Protein 22 (NMP22)
to test patients for recurrent cancer.to test patients for recurrent cancer.
It is not certain whether it is as sensitive as cystoscopy.It is not certain whether it is as sensitive as cystoscopy.
Most experts still recommend cystoscopy for diagnosis andMost experts still recommend cystoscopy for diagnosis and
follow-up of bladder cancer.follow-up of bladder cancer.

48. CA 125CA 125
Glycoprotein normally expressed inGlycoprotein normally expressed in coelomiccoelomic
epitheliumepithelium during fetal development.during fetal development.
Normal serum value: < 35 U/mL, t 1/2: 4-5 daysNormal serum value: < 35 U/mL, t 1/2: 4-5 days
Malignancies:Malignancies:
Elevated in > 90% of patients with advancedElevated in > 90% of patients with advanced
epithelial ovarian cancers,epithelial ovarian cancers,
Endo-Ca and in 40% of patients whoseEndo-Ca and in 40% of patients whose
disease is still confined to the ovary, lung cancerdisease is still confined to the ovary, lung cancer
..

49. Benign conditions- Uterine fibroidsBenign conditions- Uterine fibroids
EndometriosisEndometriosis
rupture ectopic pregnancy,rupture ectopic pregnancy,
peritonitis, appendicitisperitonitis, appendicitis
CA 125 is the standard tumor marker used to follow womenCA 125 is the standard tumor marker used to follow women
during or after treatment for epithelial ovarian cancer (theduring or after treatment for epithelial ovarian cancer (the
most common type of ovarian cancer).most common type of ovarian cancer).
High preoperative CA 125 levels correlate with advancedHigh preoperative CA 125 levels correlate with advanced
stage (III or IV) and high grade disease, serous histology, andstage (III or IV) and high grade disease, serous histology, and
the presence of ascites, but they are not a reliable predictor ofthe presence of ascites, but they are not a reliable predictor of
the likelihood of optimal cytoreductionthe likelihood of optimal cytoreduction

50. Conditions associated with an elevated serum CA 125Conditions associated with an elevated serum CA 125
concentrationconcentration
Gynecologic malignancies
Epithelial ovarian and endometrial cancers
Fallopian tube cancers and germ cell tumors
Adenocarcinoma of the cervix
Sertoli-Leydig cell tumors of the ovary
Benign gynecologic conditions
Adenomyosis
Benign ovarian neoplasms
Endometriosis
Functional ovarian cysts
Leiomyomata
Meig’s syndrome
Menstruation
Pregnancy
Ovarian hyperstimulation
Pelvic inflammation
Nongynecologic cancers
Breast
Colon
Lung
Pancreas
Nongynecologic conditions
Liver disease and cirrhosis
Colitis
Congestive cardiac failure
Diabetes
Diverculitis
Lupus
Mesothelioma
Pericarditis
Polyarteritis nodosa
Postoperative period
Previous irradiation
Renal disease
Sarcoidosis
Tuberculosis
Pleural effusion
Ascites

51. CA 15-3CA 15-3
Glycoprotein antigenGlycoprotein antigen
Normal serum value: < 25 U/mlNormal serum value: < 25 U/ml
t1/2: < 2 weekst1/2: < 2 weeks
Malignancies: Elevated in breast cancer;Malignancies: Elevated in breast cancer;
pancreas,pancreas,
gastric,gastric,
ovarian,ovarian,
lung, liver cancers

52. Ca 15-3Ca 15-3
Benign conditions:Benign conditions:
benign breast conditionsbenign breast conditions
chronic hepatitis, cirrhosis,chronic hepatitis, cirrhosis,
sarcoidosis, TB, SLEsarcoidosis, TB, SLE
CA 15-3 is used to monitor response to treatment, to detectCA 15-3 is used to monitor response to treatment, to detect
recurrence early (more sensitive than CEA)recurrence early (more sensitive than CEA)
Most sensitive in all stages of Breast CancersMost sensitive in all stages of Breast Cancers
Especially useful inEspecially useful in recurrent Breast cancer casesrecurrent Breast cancer cases

53. CA 19-9CA 19-9
intracellular adhesion moleculeintracellular adhesion molecule
Normal serum value: < 37 U/mlNormal serum value: < 37 U/ml
Malignancies:Malignancies:
Elevated in Pancreatic cancer,Elevated in Pancreatic cancer,
Colorectal cancer,Colorectal cancer,
Biliary tract cancerBiliary tract cancer
Benign conditions: Pancreatitis,Benign conditions: Pancreatitis,
Benign biliary tract diseasesBenign biliary tract diseases

54. CA 19-9CA 19-9
It has a reported sensitivity and specificity of 80 to 90 percentIt has a reported sensitivity and specificity of 80 to 90 percent
It has been proposed to differentiate benign from malignantIt has been proposed to differentiate benign from malignant
pancreatic disease, but this capability remains to be establishedpancreatic disease, but this capability remains to be established
(sensitivity and specificity of 77 and 87 percent, respectively) .(sensitivity and specificity of 77 and 87 percent, respectively) .
It will not usually detect very early disease. But it is nowIt will not usually detect very early disease. But it is now
considered the best tumor marker for following patients withconsidered the best tumor marker for following patients with
cancer of the pancreas.cancer of the pancreas.
CA 19-9 can also be used to monitor colorectal cancer, butCA 19-9 can also be used to monitor colorectal cancer, but
because it is less sensitive than the CEA test, most medical groupsbecause it is less sensitive than the CEA test, most medical groups
recommend CEA testing when following this disease instead.recommend CEA testing when following this disease instead.

55. Conditions associated with increased serum levels ofConditions associated with increased serum levels of
CA 19-9CA 19-9
Malignant
Pancreatic cancer [71-93%]
Biliary cancer (gallbladder + cholangiocarcinoma)
Hepatocellular cancer
Gastric [21-42%], ovarian, colorectal cancer [20-40%] (less often)
Lung, breast, uterine cancer (rare)
Benign
Acute cholangitis
Cirrhosis and other cholestatic diseases (including gallstones)
Very high CA 19-9 levels (eg, >1000 U/mL) are often associated with surgically
unresectable lesions,

56. CalcitoninCalcitonin
is a hormone produced byis a hormone produced by parafollicular C cells of thyroidparafollicular C cells of thyroid
glandgland
It helps regulate blood calcium levels.It helps regulate blood calcium levels.
Normal serum value: 0.2-25 pg/mlNormal serum value: 0.2-25 pg/ml
t 1/2: 12 mint 1/2: 12 min
Malignancies:Malignancies:
Elevated in medullary thyroid carcinomaElevated in medullary thyroid carcinoma
lung cancerslung cancers
Benign conditions: thyroid nodulesBenign conditions: thyroid nodules
is used in early diagnosis of inherited MTC- basal calcitonin isis used in early diagnosis of inherited MTC- basal calcitonin is
less thanless than 25 pg/mL25 pg/mL (or calcium-stimulated less than 100 pg/mL)(or calcium-stimulated less than 100 pg/mL),,
to follow patients during or after treatmentto follow patients during or after treatment

57. Chromogranin A (CgA)Chromogranin A (CgA)
& Neuron-specific enolase (NSE)& Neuron-specific enolase (NSE)
Normal serum value:Normal serum value: <76 ng/mL in men<76 ng/mL in men andand < 51 ng/mL in< 51 ng/mL in
womenwomen
Malignancies:Malignancies:
In Neuroendocrine tumors-In Neuroendocrine tumors-
Carcinoid tumorsCarcinoid tumors
Neuroblastoma,Neuroblastoma,
Small cell lung cancerSmall cell lung cancer
Pancreatic islet cell tumors,Pancreatic islet cell tumors,
Prostate cancersProstate cancers

58. Chromogranin A (CgA)Chromogranin A (CgA)
& Neuron-specific enolase (NSE)& Neuron-specific enolase (NSE)
It is probably the most sensitive tumor markerIt is probably the most sensitive tumor marker
for carcinoid tumors, being abnormal in 33 %for carcinoid tumors, being abnormal in 33 %
cases with localized disease and 66 % of thosecases with localized disease and 66 % of those
with metastatic cancer.with metastatic cancer.
The sensitivity and specificity areThe sensitivity and specificity are
approximately 92% and 96% respectively-approximately 92% and 96% respectively-
fairs better than NSEfairs better than NSE

59. Estrogen receptors/progesterone receptorsEstrogen receptors/progesterone receptors
Breast cancerBreast cancer tissues are commonly tested for these markers bytissues are commonly tested for these markers by
IHC.IHC.
Breast cancers that contain estrogen receptors are often referredBreast cancers that contain estrogen receptors are often referred
to as “ER positive,” while those with progesterone receptors areto as “ER positive,” while those with progesterone receptors are
“PR positive.”“PR positive.” (>10Fmol is +ve(>10Fmol is +ve))
Their main use is as aTheir main use is as a predictor of prognosispredictor of prognosis (survival(survival
outlook).outlook).
About 7 out of 10 breast cancers test positive for at least one ofAbout 7 out of 10 breast cancers test positive for at least one of
these markers.these markers.
These cancers tend to have a better prognosis than cancersThese cancers tend to have a better prognosis than cancers
without these receptors and are much more likely to respond towithout these receptors and are much more likely to respond to
hormonal therapy such as tamoxifen or aromatase inhibitors.hormonal therapy such as tamoxifen or aromatase inhibitors.
> 60% 0f ER + & < 10 % of ER - tumors respond.> 60% 0f ER + & < 10 % of ER - tumors respond.
Degree of positivity is proportional to grade & histology.Degree of positivity is proportional to grade & histology.

60. Epidermal growth factor receptor (EGFR)Epidermal growth factor receptor (EGFR)
Tyrosine kinase family of receptors.Tyrosine kinase family of receptors.
EGF-signalling pathways involve four known receptors- EGFR,EGF-signalling pathways involve four known receptors- EGFR,
erbB2, erbB3, erbB4.erbB2, erbB3, erbB4.
EGFR activation regulatesEGFR activation regulates
tumor cell growth & proliferation,tumor cell growth & proliferation,
DNA repair and survivalDNA repair and survival
invasion,invasion,
angiogenesisangiogenesis
metastases.metastases.

61. Epidermal growth factor receptorEpidermal growth factor receptor
Increased expression is found in a wide rangeIncreased expression is found in a wide range
of solid tumors- colorectal, breast, lungof solid tumors- colorectal, breast, lung
(NSCLC),(NSCLC), head & neckhead & neck andand pancreaticpancreatic
cancers.cancers.
Increased expression has been correlated withIncreased expression has been correlated with
disease progression, poor treatment outcome &disease progression, poor treatment outcome &
poor survival.poor survival.
Targeted therapies-Targeted therapies- geftinib, erlotinib,geftinib, erlotinib,
cetuximab,cetuximab, ABX-EGF are directed againstABX-EGF are directed against
these receptors.these receptors.

62. HER-2/neu (c-erbB-2)HER-2/neu (c-erbB-2)
Over-expressed in someOver-expressed in some breast cancerbreast cancer tissues, also intissues, also in ovarianovarian,,
gastric cancersgastric cancers..
About 1 in 3 people with breast cancer test positive for HER-2/neuAbout 1 in 3 people with breast cancer test positive for HER-2/neu
..
Its main use is as aIts main use is as a predictor of prognosispredictor of prognosis (survival outlook).(survival outlook).
Those whose cancers are positive for this marker respond well toThose whose cancers are positive for this marker respond well to
anthracycline based chemotherapyanthracycline based chemotherapy vs CMF and generally havevs CMF and generally have
been thought to have a less favorable outlook.been thought to have a less favorable outlook.
However, these cancers are more likely to respond toHowever, these cancers are more likely to respond to
immunotherapy withimmunotherapy with trastuzumab (Herceptintrastuzumab (Herceptin)- antibody that)- antibody that
works against the HER-2/neu receptor on breast cancer cells.works against the HER-2/neu receptor on breast cancer cells.

63. ImmunoglobulinsImmunoglobulins
Malignancies: blood (as well as in the urine) levels elevated inMalignancies: blood (as well as in the urine) levels elevated in
multiple myeloma and Waldenstrom macroglobulinemiamultiple myeloma and Waldenstrom macroglobulinemia..
Detected by protein electrophoresis- the globulins (also calledDetected by protein electrophoresis- the globulins (also called
monoclonal proteins or M proteins) stick together and form amonoclonal proteins or M proteins) stick together and form a
monoclonal "spike" (M spike) on the readout of the test.monoclonal "spike" (M spike) on the readout of the test.
The level of the spike is important, because older people may showThe level of the spike is important, because older people may show
low levels of a spike without havinglow levels of a spike without having myeloma ormyeloma or
macroglobulinemiamacroglobulinemia..
Immunoglobulin levels are used to follow response to treatment.Immunoglobulin levels are used to follow response to treatment.

64. Lactate dehydrogenaseLactate dehydrogenase
Serum LDH concentrations are elevated in 30 to 80 percent of menSerum LDH concentrations are elevated in 30 to 80 percent of men
withwith pure seminomapure seminoma and in 60 percent of those withand in 60 percent of those with
nonseminomatous tumors, also innonseminomatous tumors, also in lymphomaslymphomas ..
LDH is a less sensitive and less specific tumor marker than beta-LDH is a less sensitive and less specific tumor marker than beta-
hCG or AFP for men with NSGCTs, but it may be the only markerhCG or AFP for men with NSGCTs, but it may be the only marker
that isthat is elevated in seminomaselevated in seminomas..
In addition, a significantly elevated serum LDH has independentIn addition, a significantly elevated serum LDH has independent
prognostic value in men with advanced seminoma.prognostic value in men with advanced seminoma.
Serum LDH is neither a sensitive nor specific indicator of diseaseSerum LDH is neither a sensitive nor specific indicator of disease
recurrence in men with GCTs. As a result, it is not a useful serumrecurrence in men with GCTs. As a result, it is not a useful serum
marker tomarker to monitor for disease relapsemonitor for disease relapse..

65. MelanomaMelanoma
 TyrosinaseTyrosinase
 Use RT-PCR to detect hematogenous spread ofUse RT-PCR to detect hematogenous spread of
melanoma cells from a solid tumor inmelanoma cells from a solid tumor in
peripheral bloodperipheral blood
 S100B proteinS100B protein
 For confirmation of amelanotic malignantFor confirmation of amelanotic malignant
melanoma in immunohistologymelanoma in immunohistology
 ↑↑in 70% with stage IV metastasized melanomain 70% with stage IV metastasized melanoma
 MIA (melanoma inhibitory activity)MIA (melanoma inhibitory activity)
 Preoperation: 59% at stage III, 89% at stage IVPreoperation: 59% at stage III, 89% at stage IV

66. Thyroid CancerThyroid Cancer
 ThyroglobulinThyroglobulin ：：
 Tissue-specificTissue-specific, glycoprotein produced by thyroid, glycoprotein produced by thyroid
follicular cellsfollicular cells
 normal: <60 ug/Lnormal: <60 ug/L
 Also increased in breast or lung cancerAlso increased in breast or lung cancer
 ThyrocalcitoninThyrocalcitonin ：：
 Produced by thyroid C cells and medullary thyroidProduced by thyroid C cells and medullary thyroid
cancercancer
 normal:normal: <100 ng/L or <29 p mole/L<100 ng/L or <29 p mole/L
 Effective inEffective in screen patientsscreen patients with 1with 1stst
degree relativesdegree relatives
affected by medullary thyroid cancer and multipleaffected by medullary thyroid cancer and multiple
endocrine neoplasia type 2endocrine neoplasia type 2

67. Cervical Sqamous CellCervical Sqamous Cell
CarcinomaCarcinoma
 Squamous cell carcinoma antigenSquamous cell carcinoma antigen ((SCCSCC))
 Normal value:Normal value: <2<2 ng/mlng/ml
 Not sensitive enough for screening early –stageNot sensitive enough for screening early –stage
carcinomacarcinoma
 Prognosis, monitorPrognosis, monitor

68. Tumor Markers In Common UseTumor Markers In Common Use
Use of tumor marker
Tumor
marker
Primary tumor(s) Screening Diagnosis Follow-up after primary
treatment
Monitoring of
treatment response
CA 27.29 Breast cancer No No Consider in patients at
high risk for recurrence;
obtain CA 27.29 level
every 4 to 6 months.
Helpful
CEA Colorectal cancer No No In patients at high risk for
recurrence, obtain CEA
level every 2 to 3 months
for at least 2 years.
Very helpful
CA 19-9 Pancreatic cancer,
biliary tract cancer
No Selected
pancreatic
masses
No Helpful
AFP Hepatocellular
carcinoma,
nonseminomatou
s germ cell tumor
No* Poorly
differentiated
cancer of
unknown
primary;
patients with
cirrhosis and
a liver mass
In patients treated for
nonseminomatous germ
cell tumor, obtain AFP
and β-hCG levels every 1
to 2 months for 1 year,
then quarterly for 1 year,
and less frequently
thereafter.
Essential in
patients treated for
nonseminomatous
germ cell tumor;
very helpful in
patients treated for
hepatocellular
carcinoma

69. Use of tumor marker
Tumor
marker
Primary tumor(s) Screening Diagnosis Follow-up after primary
treatment
Monitoring of
treatment
response
β-hCG Nonseminomato
us germ cell
tumor,
gestational
trophoblastic
disease
No Poorly
differentiated
cancer of
unknown
primary;
gestational
trophoblastic
disease
Nonseminomatous germ
cell tumor: see AFP above.
In patients treated for
gestational trophoblastic
disease, obtain b-hCG level
once a month for 6 to 12
months.
Essential in
patients treated
for non-
seminomatous
germ cell tumor
or gestational
trophoblastic
disease
CA 125 Ovarian cancer No† Adjunct for
diagnosis of
pelvic mass in
postmenopausal
women;
malignant ascites
in women with
cancer of
unknown primary
Obtain CA 125 level every 3
months for 2 years, then
less frequently.
Very helpful
PSA Prostate cancer Yes Adenocarcinoma
of unknown
primary; widely
positive bone
scan and prostate
mass
Obtain PSA level every 6
months for 5 years, then
annually. Any detectable
PSA after radical
prostatectomy indicates
recurrence.Three
consecutive PSA elevations
after radiation therapy
indicate recurrence.
Very helpful

70. Immunoperoxidase tumor stainingImmunoperoxidase tumor staining
Most widely available specialised technique for classification ofMost widely available specialised technique for classification of
neoplasmsneoplasms
Can be done on fresh tissue, cytology smears, formalin-fixedCan be done on fresh tissue, cytology smears, formalin-fixed
paraffinised tissueparaffinised tissue
Antibodies (monoclonal/ polyclonal) are directed at cellAntibodies (monoclonal/ polyclonal) are directed at cell
components/ products, which includecomponents/ products, which include
enzymes (PSA, NSE),enzymes (PSA, NSE),
normal tissue components (keratin, desmin, vimentin,normal tissue components (keratin, desmin, vimentin,
CLA), hormones & hormone receptors (ER, PgR),CLA), hormones & hormone receptors (ER, PgR),
onco-fetal antigens (onco-fetal antigens (αα-fetoprotein, AFP), CEA, S-100-fetoprotein, AFP), CEA, S-100
protein etc.protein etc.

71. Immunoperoxidase tumor staining patterns useful in differentialImmunoperoxidase tumor staining patterns useful in differential
diagnosis of poorly differentiated neoplasmsdiagnosis of poorly differentiated neoplasms
Tumor type Immunoperoxidase staining
LYMPHOMA CLA (+), rare false (-); EMA occasionally (+); All other stains (-)
SARCOMA
Mesenchymal
Rhabdomyosarcoma
Angiosarcoma
Gastrointestinal stromal tumor
Vimentin (+); Epithelial stains usually (-)
Desmin (+)
Factor VIII antigen (+)
CD 117 (c-kit) (+)
MELANOMA S-100, vimentin, HMB45 (+); NSE often (+)
Synaptophysin (-); Epithelial stains (-)

72. D/D of immunostaining for cytokeratin (CK) 7 and 20D/D of immunostaining for cytokeratin (CK) 7 and 20
.
CK7+ CK20+ CK7+ CK20- CK7- CK20+ CK7- CK20-
Urothelial tumors
Mucinous ovarian
cancer
Pancreatic cancer
Non-small cell
lung cancer
Small cell lung
cancer
Breast cancer
Endometrial
cancer
Nonmucinous
ovarian cancer
Mesothelioma
Squamous cancer
of cervix
Colorectal cancer
Merkel cell cancer
Hepatocellular
cancer
Renal cell cancer
Prostate cancer
Squamous cell
lung cancer
Head and Neck
cancer

73. Case 1Case 1
 A 35-year-old healthy male with a past history ofA 35-year-old healthy male with a past history of
cryptorchidismcryptorchidism repaired at age 5 presented withrepaired at age 5 presented with painlesspainless
enlargement of the left testisenlargement of the left testis. A testicular ultrasound. A testicular ultrasound
examination revealed a soft tissue mass without a cysticexamination revealed a soft tissue mass without a cystic
component.component.
 What markers will you do?What markers will you do?
A.A. AFPAFP
B.B. HCGHCG
C.C. LDHLDH
D.D. All of the aboveAll of the above
E.E. None of the aboveNone of the above

74. Case 1Case 1
 Answer:Answer: DD
 Serum HCG = 90 mU/mL (< 5Serum HCG = 90 mU/mL (< 5
mlU/mL)mlU/mL)
 AFP = 7 ng/mL (< 5.4 ng/mL).AFP = 7 ng/mL (< 5.4 ng/mL).
 Radical left orchiectomyRadical left orchiectomy
Final Diagnosis: Seminoma, classic type

75. Case 2Case 2
 69 y male with long standing anemia & positive69 y male with long standing anemia & positive
occult blood test presented with right iliac mass.occult blood test presented with right iliac mass.
 The marker useful in the diagnosis is/areThe marker useful in the diagnosis is/are
AA.. AFPAFP
B. LDHB. LDH
C. CEAC. CEA
D. All of the aboveD. All of the above
E. None of the aboveE. None of the above

76. Case 2Case 2
 Answer: EAnswer: E
 Right hemicolectomyRight hemicolectomy
Final Diagnosis: Mod. Diff. adenocarcinoma

77. Marker For ColorectalMarker For Colorectal
CancerCancer
CEACEA
(Only for follow-up and monitoring)(Only for follow-up and monitoring)

78. Case 3Case 3
 A 63 male presented withA 63 male presented with urinary hesitancy,urinary hesitancy,
frequency, and nocturiafrequency, and nocturia. Digital rectal exam. Digital rectal exam
revealed a large, nodular, and rubbery prostate glandrevealed a large, nodular, and rubbery prostate gland
withwith focal hard regionsfocal hard regions. Prostatic biopsies were. Prostatic biopsies were
performed.performed.
 The most useful marker isThe most useful marker is
A.A. AFPAFP
B. Alkaline phosphataseB. Alkaline phosphatase
C. PSAC. PSA
D. CEAD. CEA
E. CA 125E. CA 125

79. Case 3Case 3
 Answer:Answer: CC
 Serum PSA = 6 ng/mL (0-4Serum PSA = 6 ng/mL (0-4
ng/mL)ng/mL)
 Biopsy: +Biopsy: +
 Radical ProstatectomyRadical Prostatectomy
Final Diagnosis: Adenocarcinoma, GS: 7 (3+4)

80. Case 4Case 4
 52-year-old former dancer goes to her internist because of52-year-old former dancer goes to her internist because of
vague abdominal pain and a feeling of fullnessvague abdominal pain and a feeling of fullness. The. The
physician notes abdominal fullness with a fluid wave,physician notes abdominal fullness with a fluid wave,
consistent with ascites. He also performs a pelvicconsistent with ascites. He also performs a pelvic
examination. Aexamination. A 10-cm left adnexal mass10-cm left adnexal mass is easily felt.is easily felt.
 The following marker is of prognostic useThe following marker is of prognostic use
A. CA 125A. CA 125
B. PSAB. PSA
C. CA 27.29C. CA 27.29
D. PAPD. PAP
E. None of the aboveE. None of the above

81. Case 4Case 4
 AnswerAnswer:: AA
 Ascites: + for malignantAscites: + for malignant
cellscells
 Laparotomy and stagingLaparotomy and staging
Final Diagnosis:
Papillary serous cyst adeno
carcinoma

82. At the end of therapy –At the end of therapy –
beware the misleadingbeware the misleading
Does not mean cureDoes not mean cure
Does not mean complete remissionDoes not mean complete remission
May not even mean improvementMay not even mean improvement
If we use the number to reassure, weIf we use the number to reassure, we
have to manage the anxiety with thehave to manage the anxiety with the
rising numberrising number
“normal”

83. Beware the “mysteries”Beware the “mysteries”
Elevated marker with NEDElevated marker with NED
: BHCG with creatinine elevated: BHCG with creatinine elevated
Elevated marker with no cancerElevated marker with no cancer
eg: CA125 or CEAeg: CA125 or CEA
Multiple markers elevatedMultiple markers elevated
Marker falling, mass increasingMarker falling, mass increasing
There is a role for clinical judgement!There is a role for clinical judgement!

84. Tumor Markers - Recent AdvancesTumor Markers - Recent Advances
 Shortcomings of “conventional markers” lead to “advancedShortcomings of “conventional markers” lead to “advanced
molecular techniques” based onmolecular techniques” based on
1. Genetic hallmarks of malignancy rapidly determined1. Genetic hallmarks of malignancy rapidly determined
2. Tumor Molecular aberrations reflected in2. Tumor Molecular aberrations reflected in
plasma/serum/body fluidsplasma/serum/body fluids
3. Extremely small amounts of nucleic acids can be3. Extremely small amounts of nucleic acids can be
measured (PCR, RT-PCR)measured (PCR, RT-PCR)

85. Tumor Markers - RecentTumor Markers - Recent
AdvancesAdvances
 4. High resolution protein separation4. High resolution protein separation
(2 D polyacrylamide gel electrophoresis(2 D polyacrylamide gel electrophoresis
technology)technology)
Rapid identification of separated proteinsRapid identification of separated proteins (mass(mass
spectrometry)spectrometry)
proteomicsproteomics (study of proteins)(study of proteins) feasiblefeasible

86. Tumor Markers - Recent AdvancesTumor Markers - Recent Advances

87. Tumor Markers - Recent AdvancesTumor Markers - Recent Advances
 GenomicsGenomics
 The study of genes and their function.The study of genes and their function.
 ProteomicsProteomics
 The study of the full set of proteins encoded by aThe study of the full set of proteins encoded by a
genome.genome.

88. Tumor Markers - Recent AdvancesTumor Markers - Recent Advances
 Molecular Classification of Circulating TumorMolecular Classification of Circulating Tumor
MarkersMarkers
1. DNA markers1. DNA markers
2. RNA markers2. RNA markers
3. Protein markers3. Protein markers

90. Tumor Markers - Recent AdvancesTumor Markers - Recent Advances
DNA MarkersDNA Markers
Exogenous
(viral)
EBV – NPC
HPV – Cervical Ca.
Endogenous
Epigenetic
Genetic
P15/16 – Liver Ca.
Nuclear
Mitochondrial
Kras – Pancreatic Ca.
ND4 gene – Bladder Ca.

91. Tumor Markers - Recent AdvancesTumor Markers - Recent Advances
RNA MarkersRNA Markers
Exogenous
(viral)
Endogenous
Cell Based
Cell Free
PSA mRNA – Prostate Ca.
CK20 mRNA – Breast Ca.
Tyrosine mRNA – Melanoma
Telomerase mRNA – Pancreatic Ca.
EBV coded mRNA - NPC

92. Tumor Markers - Recent AdvancesTumor Markers - Recent Advances
Protein MarkersProtein Markers
Protein
Native Protein
Glycan
Altered
Ectopic
PSA – Prostate Ca.
CEA – Colon Ca.
Monosialylated AFP - HCC
ACTH – Small cell Ca. Lung

93. Take Home MessageTake Home Message
 Screening Marker: PSA + DREScreening Marker: PSA + DRE
 Staging/Prognosis/Follow-upStaging/Prognosis/Follow-up
1.1. Germ cell: AFP,Germ cell: AFP, ββ hCG, LDHhCG, LDH
2.2. Colorectal: CEAColorectal: CEA
3.3. Breast: CA15.3, CA27.29, CEABreast: CA15.3, CA27.29, CEA
4.4. Ovary: CA125, CEA, CA19.9, hCG, AFPOvary: CA125, CEA, CA19.9, hCG, AFP

94. Take Home MessageTake Home Message
 Staging/Prognosis/Follow-upStaging/Prognosis/Follow-up
5. Prostate: PSA, PAP5. Prostate: PSA, PAP
6. Pancreas: CA19.96. Pancreas: CA19.9
7. Neuroendocrine: NSE, Calcitonin, VMA,7. Neuroendocrine: NSE, Calcitonin, VMA,
uCatecholamine.uCatecholamine.
8.8. Endocrine: TG, PTH, Pituitary hormonesEndocrine: TG, PTH, Pituitary hormones
9.9. Gestational TB disease:Gestational TB disease: ββ hCGhCG

95. Take Home MessageTake Home Message
 PleasePlease remember the followingremember the following points whenpoints when
ordering a serum tumor marker;ordering a serum tumor marker;
1.1. Never rely on a single testNever rely on a single test
2.2. Recommend a panel of markersRecommend a panel of markers
3.3. In serial testing, use the same lab with same assayIn serial testing, use the same lab with same assay
kitkit
4.4. Consider the half life of the marker whenConsider the half life of the marker when
interpreting the test resultinterpreting the test result
5.5. Consider how the tumor marker is removed orConsider how the tumor marker is removed or
metabolized from the blood circulationmetabolized from the blood circulation

96. Sensitivity & SpecificitySensitivity & Specificity
 None of current markers 100% S & SNone of current markers 100% S & S
MarkerMarker SensitivitySensitivity SpecificitySpecificity
PSA (prostate)PSA (prostate) 90%90% 25%25%
CA15.3 (breast) 23%CA15.3 (breast) 23% 69%69%
AFP (liver)AFP (liver) 39-64%39-64% 76-91%76-91%
 Current Approach to increase S & SCurrent Approach to increase S & S
1. To improve on a currently used marker (free PSA-benign)1. To improve on a currently used marker (free PSA-benign)
2. To discover and validate new markers2. To discover and validate new markers
3. To use a panel of tumor markers3. To use a panel of tumor markers

97. REFERENCESREFERENCES
 BAILEY & LOVE’S- SHORT PRACTISE OFBAILEY & LOVE’S- SHORT PRACTISE OF
SURGERYSURGERY
 SABISTON TEXTBOOK OF SURGERYSABISTON TEXTBOOK OF SURGERY
 MASTERY OF SURGERY by FischerMASTERY OF SURGERY by Fischer
 OXFORD TEXTBOOKOF SURGERYOXFORD TEXTBOOKOF SURGERY
 TUMOUR ESSAY – A.BURKTUMOUR ESSAY – A.BURK
 INTERNET JOURNALSINTERNET JOURNALS
 RECENT ADVANCES- WOLTERS KLUWERRECENT ADVANCES- WOLTERS KLUWER
 RECENT ADVANCES- RSGRECENT ADVANCES- RSG

98. ConclusionsConclusions
 Tumor markers have changed the diagnosis and management ofTumor markers have changed the diagnosis and management of
patients with malignancies.patients with malignancies.
 They play a vital role in staging testicular cancers, screening forThey play a vital role in staging testicular cancers, screening for
prostate cancers, prognosis in colorectal cancers.prostate cancers, prognosis in colorectal cancers.
 They are being evaluated in screening for HCC, epithelialThey are being evaluated in screening for HCC, epithelial
ovarian cancers.ovarian cancers.
 Further research is needed to refine the role of these markers inFurther research is needed to refine the role of these markers in
management of cancer patients.management of cancer patients.
 Recent advances in technology provide additional malignantRecent advances in technology provide additional malignant
tumor markers in the immediate futuretumor markers in the immediate future

99. HELLO– ANY QUESTIONSHELLO– ANY QUESTIONS

100. The best time to plant a tree wasThe best time to plant a tree was
20 years ago . . .20 years ago . . .
. . . the second best time is today.. . . the second best time is today.
THANK YOUTHANK YOU

101. THANKSTHANKS
THANKS