7. People with a Cancer of Unknown Primary
(CUP) have been diagnosed with some
form of metastatic cancer, but the primary
cancer cannot be located
8. • Cancer of unknown primary means that the
original site, the primary, is either too small to
find or has died. The aggressive remaining
cancer spreads throughout the body. Though
occasionally there are remarkable
improvements, and even the rare cure with
chemotherapy, it generally has a grim prognosis.
CUP is often advanced when discovered and
resistant to treatment. Occasionally, this illness
responds to medicine, which at times can extend
life, but even then it is often not curable
9. When a person is diagnosed with cancer that has
spread within the body (metastatic cancer) the
primary site – the place in the body where the
cancer started – is not always obvious. Finding
the genetic origin of the cancer is important to
define the best treatment. When the origin of the
cancer is not identified with confidence, after
initial tests, this is described as Cancer of
Unknown Primary or CUP
For some CUP patients the primary cancer will
remain unknown and will never be identified
10. Cancers of unknown primary or occult primary
malignancies are tumors that have metastasized from an
unknown primary source, and make up approximately
2% - 6% of all cancer cases.
Conventional methods used to aid in the identification of
the origin of a cancer of unknown primary malignancy
include a thorough history and physical examination,
computed tomography (CT) scans of the chest,
abdomen, and pelvis, routine laboratory studies; and
targeted evaluated of specific signs and symptoms.
Identifying the primary origin of a tumor can dictate
cancer specific treatment, expected outcome, and
prognosis
11.
12.
13. Median survival ranges from 4 to 11o/o.
1.3 and 5-year survival are 23o/o, 11o/o and
6o/o respectively.
Most do not benefit from chemo.
14. Molecular profiling of cancers of unknown primary
(CUP): paradigm shift in management of CUP.
Molecular profiling aimed at detection of biomarkers.
Multiplatform approach…
IHC,sequencing(Sanger,NGS),qPCR,FISH,dISH
Predictive biomarker molecular profiling of CUP
identifies actionable targets in ~ 80% of all cases.
15. Microarray-based gene expression testing (e.g., the Pathwork® Tissue
of Origin Test), also known as gene expression profiling, is being
offered by the manufacturer as being possibly useful in identifying
the origin of cancers of unknown primary malignancy. The test
measures the expression of more than 1,500 genes and compares
the similarity of the gene expression profile of a cancer of unknown
primary to a database of known profiles from 15 tissues with more
than 60 histologic morphologies. The test uses a proprietary
Pathchip® microarray and runs on the Affymetrix GeneChip®
system. The report generated for each tumor consists of a similarity
score, which is a measure of similarity of the gene expression profile
of the specimen to the profile of the 15 known tumors in the
database. Scores range from 0 (very low similarity) to 100 (very high
similarity), and sum to 100 across all 15 tissues on the panel. If a
single similarity score is greater than or equal to 30, it indicates that
this is likely the tissue of origin. If every similarity score is between 5
and 30, the test result is considered indeterminate, and a similarity
score of less than 5 rules out that tissue type as the likely origin.
16. The Pathwork Tissue of Origin test (Pathwork
Diagnostics) uses measurements of the levels of
2,000 different mRNAs to determine the most
likely tissue of origin for an unknown sample
from among a panel of 15 different tumors. The
similarity score test result is considered
diagnostic if the highest similarity score is
greater than 20, and this report confirms the cell
of origin with99% certainty.
17.
18.
19. WHAT ABOUT DEALING WITH PATIENTS
WHO REQUIRE ADMISSION?
Admit patient under an appropriate team (Cancer
center, General Medicine hospital, General
Surgery hospital…ie. Each area would have a
responsible team).
20.
21.
22.
23.
24.
25.
26. CGP can identify novel treatment paradigms and
suggested that early testing may have utility in
CUP management. This study illustrates some
important considerations in the diagnostic
workup and management of patients with CUP.
27. FROM IMMUNOHISTOCHEMISTRY TO GENE EXPRESSION
PROFILING.
Immunohistochemistry analysis is a vital component in the investigation
of CUP cancers. However, the analysis has limitations because
markers for CUP are not uniformly site specific or sensitive.
When the initial evaluation remains ambiguous as to theprimary cell of
origin, the IHC analysis did not appear toprovide clarity for the
primary site.
Several commercial molecular gene expression–based assays (Tissue
of Origin test [Pathwork Diagnostics], CancerType ID
[BioTheranostics, San Diego,CA], and MiRview Mets test [Rosetta
Genomics, Philadelphia,PA; Rehovot, Israel]) for CUP are available
with prediction accuracies in known primary cancers of 80% to 90%.
Genomic testing is becoming an integral tool used in directing future
therapeutic decisions in patients with cancers of unknown origins.
28.
29.
30.
31.
32.
33. Cancer of unknown primary site (CUP) is a well recognised clinical
disorder, accounting for 3–5% of all malignant epithelial
tumours. CUP is clinically characterised as an aggressive
disease with early dissemination. Diagnostic approaches to
identify the primary site include detailed histopathological
examination with specific immunohistochemistry and
radiological assessment. Gene-profiling microarray diagnosis
has high sensitivity, and patients' outcomes are improved by its
clinical use. Metastatic adenocarcinoma is the most common
CUP histopathology (80%). CUP patients are divided into
subsets of favourable (20%) and unfavourable (80%)
prognosis. Favourable subsets are mostly given locoregional
treatment or systemic platinum-based chemotherapy.
Responses and survival are similar to those of patients with
relevant known primary tumours. Patients in unfavourable
subsets are treated with empirical chemotherapy based on
combination regimens of platinum or taxane, but responses
and survival are generally poor
