Tumor markers in diagnosis and prognosis of colorectal cancer

1. Kiran Malbul
NAIHS

2. What are tumor markers ?
• Also Called as biomarkers
• Oncoproteins or mutated forms of proteins produced by cancer cells
or by other cells in response to cancer or by noncancerous conditions
too.
• Most are tumors antigens
• Can be found in the blood, urine, stool, tumor tissue or other tissues
or bodily fluids of some patients with cancer.
• Associated with only one type of cancer, whereas others are
associated with two or more cancer types

3. Tumor markers associated with colorectal cancer
Markers found in the blood : 1) CarcinoEmbryonic Antigen (CEA)
2) CA 19-9
3) Circulating tumor cells of epithelial origin
(CELLSEARCH®)
Markers found in tumor tissue: 1) Microsatellite Instability (MSI)
2) oncogenes mutation: BRAF mutations
3) Tumor suppressor gene mutations: K-RAS,p-53
4) Tumor M2-PK

4. CarcinoEmbryonic Antigen (CEA)
• What ?  Glycoprotein used for cell adhesion.
• When ?  1.Production ceases before birth.
2.Colorectal carcinoma, lung carcinoma, gastric carcinoma,
pancreatic carcinoma and breast carcinoma
(a non-specific tumor marker)
• What else ?  may also increase in heavy smoking, non-neoplastic conditions
like pancreatitis, cirrhosis, COPD
(Not reliable alone for diagnosis of cancer)
• Sample ?  through blood
• Sensitivity  80.43% Specificity 75% (lower in early stages)

5. Contd..
• Normal level ?  <2.5ng/ml
• During cancer ? upto 20ng/ml
• Detection ?  detected by monoclonal antibody arcitumomab

6. CA 19-9
• What ?  A cancer antigen 19-9 or also known as carbohydrate antigen 19-9
• When ?  Level raises in GI cancer ; colorectal cancer, esophageal cancer
and hepatocellular cancer (a non-specific tumor marker)
• What else? May also increase in pancreatitis, cirrhosis, and diseases and
obstruction of the bile ducts. ( Not used alone for diagnosis and
screening)
• Sample ?  Blood
• Sensitivity  69.57% Specificity 61.11%
• Normal  <37 U/ml

7. Microsatellite Instability (MSI)
• What ? It is defined as appearance of abnormality long or short
microsatellite genes in individual’s DNA leading to instability.
• How ?  It is a condition manifested by damaged DNA repair gene due to
mutations. loss of DNA repair gene  Repetitive DNA sequence
 Normal sequence of gene is broken in microsatelliteinstability
• Result  Such microsatellite insertion in Tumor suppressor gene coding cause
1. uncontrolled cell division
2. tumor growth

8. Oncogene and tumor suppressor gene mutations
• Oncogenes : BRAF mutations
• Tumor suppressor gene mutations : K-RAS gene mutations  10-50% of cases
P53 gene mutations  70-80% of cases
• Tissue analyzed  Tumor tissues

9. Tumor M2-PK
• What ?  dimeric form of the pyruvate kinase isoenzyme typeM2 and a key
enzyme within tumor metabolism.
• When ?  colorectal cancer
• Sample ?  feces
• Sensitivity 85% Specificity95%
• What else ?  1. Advance in the early detection of colorectal carcinomas
2. Non-invasive medical checkups

10. So, when are they useful ?
Screening
Diagnosing
Staging
Prognosis
Guidance
Monitoring
Therapy

11. 1. Screening and diagnosis : .To identify early cancer risk
.Done with combination of other tests like stool test,
occult blood test, radiographic studies and CT scan
2. Staging : . To assess the stage of the cancer
3. Prognosis : . To predict the outcome
4. Guidance : . To guide the course of treatment
5. Monitoring : . To evaluate response to treatment
6. Therapy : . To target and plan the therapy

12. What are their limitations?
• Lack of high specificity  false positives
• Lack of high sensitivity  false negatives
• Benign tumors  positive CA-125 or CEA
• Sometimes, noncancerous conditions can cause the levels of certain tumor
markers to increase e.g. Raised CEA in smokers as well.
• Small amount in normal people.
• Not higher levels with some cancers .
• Absence of tumor markers for every type of cancers.

13. Thank you !!!