TUMOUR MARKERS AND

THE SURGEON
GUIDE- PROF. S.MAJUMDAR
DR.P.S.DUTTA
PRESENTED BY DR. IPSEET MISHRA

DEFINITION
Substances determined in the tumour
tissue (qualitative) or in serum or other
body fluids (quantitative) of a patient with
neoplastic disease that provide information
about biological characteristics of the
tumour.

What are Tumor Markers

Biological substances synthesized and
released by cancer cells themselves
or produced by the host in response to the
presence of tumor
Most tumor markers are proteins
Detected in a solid tumor, in circulating
tumor cells in peripheral blood, in serum,
lymph nodes, in bone marrow, or in other
body fluid (urine, stool, ascites)

When are they useful ?

Screenin
g

Early
Detection

Diagnosi
s

Monitor

The Various Putative Utilities

1.
2.
3.
4.
5.
6.
7.

Screening To identify early cancer risk

Diagnosis
To corroborate the diagnosis
Staging
To assess & stratify the risk
Prognosis To predict the outcome
Localization To locate the primary
Therapy
To target the therapy
Surveillance
To detect recurrence in FollowUp
8. Monitoring
To evaluate response to Rx.

Tumor Markers - Drawbacks

1.
2.
3.
4.
5.
6.
7.
8.

Cancer heterogeneity
Lack of Specificity false positives
Lack of Sensitivity - false negatives
Benign diseases - positive CA 125 or CEA
Smokers have raised CEA
Normal persons also have small amounts
Higher levels only with large tumor volume
Some cancers never have higher levels

Tumor Markers

Antigens

Hormones

TUMOR
Enzymes

Tissue
Specific

Specific Classes of Tumor

Markers
Enzymes (PSA, NSE, VMA, HVA)
Cell membrane receptors (ER, PR)
Tumor antigens (CEA, AFP)
Antibodies (IgA, IgG, IgM, IgD)
Antigens (p53, ki-62)
CA-specific proteins(CA 19-9, CA
124)
Gene mutation products (BR CA 1,
2)

Tissue-specific proteins (PSA, hCG)

Special hormones (b-hCG, hCG)
Catecholamines (VMA, HVA, ACTH)
Polyamines
Cytoplasmic / Nucleic material (DNA)
Products of cell turn-over (TNF)
Cellular modulators (ki-62, c-erb-2)

How to Detect Tumor Markers?

ELISA
Immuno-histochemistry (IHC)
Polymerase chain reaction (PCR)
Fluorescence in situ hybridization
(FISH)
Cluster Kits ( All-in-One Kit)

Detects profiles

Patterns

Prototypes

Constellations

Tumor Markers: PSA

Prostate Specific Antigen(PSA) is a glycoprotein

Ideal as a tumor marker, high tissue specificity
High sensitivity for prostate cancer
Also elevated in BPH & prostatitis
Useful in
Dx. & follow up of prostate Ca, Prognostic factor
To monitor recurrence & response to treatment
? For screening of prostate cancer along with DRE

 Free PSA PSA not bound to the plasma anti

proteases 1-antichymotrypsin & 2macroglobulin
An in ratio of free/total PSA is associated with
increased probability of prostate cancer
97% specificity, 96% sensitivity for prostate Ca
For population screening and diagnosis an
increase of 0.75 ng/ml per year in any given
patient has high sensitivity and specificity for
prostate cancer vs BPH, especially when
combined with DRE and TRUS

Tumor Markers: CA-125

80% of non-mucinous ovarian cancer detected by
the monoclonal antibody to CA-125. Serous >
Endometriod, Clear cell > mucinous
Useful in monitoring ovarian Ca recurrence & Rx. For
follow up, an increase may predict recurrent
disease, precedes clinical recurrence by months
Correlates with tumor bulk.

 Elevated in Ovarian, Endometrial, Pancreatic,

Lung, Breast, Colon cancers
Also in Menstruation, Pregnancy, Endometriosis,
PID and other gynecological and non
gynecological conditions.
Screening of high risk population (BRCA1-2
Carriers); Not useful for routine screening

Tumor Markers: AFP

A serum fetal glycoprotein synthesized by the liver, yolk sac,
gastrointestinal tract
In Hepatocellular Cancer: It is diagnostic (>500) and also
useful for screening of high risk population (HBV, HCV)
Benign conditions: hepatic parenchymal inflammation,
hepatic necrosis, pregnancy, primary biliary cirrhosis, EHBO
give positive test.
Testicular germ cell tumor (embryonal or endodermal):
For Diagnosis, Prognosis, to monitor recurrence & response
The absolute AFP level correlates with tumor bulk
Raised in Cancers of pancreas, colon, stomach &
bronchogenic Ca

Tumor Markers: CEA

Complex glycoprotein associated with the plasma
membrane of tumor cells
Elevated specially in Colon cancer, MTC, AdenoCa
uterus
Also in Pancreatic, Gastric, Lung, breast & Ovarian Ca
Also in cirrhosis, inflammatory bowel disease, chronic
lung disease, pancreatitis, fibrocystic breast disease
19% of smokers, 3% of healthy population
Normal pre Rx CEA indicates no metastasis
Not satisfactory for screening for a healthy population
Good for monitoring recurrence & to monitor Rx.

Tumor Markers: CA 19-9

Elevated in 20-40% colonic Ca , 21-42% gastric

Ca and in 71-93% pancreatic Ca cases

For D/D of benign from malignant disease
Dx, FU, Relapse - 70% specificity & 90%
sensitivity
It is a mucin, does not during pregnancy
Monitor patients who do not express CA 125,
mucinous (76%) > serous (27%)

eta HCG
Glycoprotein synthesized by syncytiotrophoblastic
cells of normal placenta
Serum and urine HCG in early gestation and peak
in the first trimester (60~90 days)
Elevated in Gestational trophoblastic disease (a
progressive rise in after 90 days of gestation
highly suggestive), choriocarcinoma
Elevated in testicular cancer, HCG after surgery
Monitor treatment response, relapse & recurrence

Breast Cancer and ER

2 isoforms ERa and ERb
ERa better prognosis, predictor of relapse
useful when deciding on adjuvant hormone
treatment
As diagnostic marker when it is a primary unknown
tumor
ERb Good prognostic factor, correlates with low
grade and negative axillary LN status

Breast Cancer Oncogenes

HER-2/neu oncogene (using monoclonal
antibody) - over expression related to poor
prognosis in breast cancer
Oncogene c-erbB-2 gene over expressed in
30% of breast cancers, correlation between
cerbB-2 gene positivity, positive axillary node
status, reduced time to relapse and reduced
overall survival
BRCA1 gene on chromosome 17q familial
breast-ovarian cancer syndrome, and breast
cancer in early-onset breast cancer families
high risk screening

Breast Cancer and CA15-3

in 20% with localized breast cancer, ~80% with
metastatic disease, esp. if with bone involvement
To monitor Rx. & to detect recurrence in BR Ca
Specificity of 86%, sensitivity of 30%
Also in gastric, pancreatic, cervical & lung
cancer

Melanoma
Tyrosinase
Use RT-PCR to detect hematogenous spread of
melanoma cells from a solid tumor in peripheral
blood
S100B protein
For confirmation of amelanotic malignant
melanoma by immunohistology
in 70% with stage IV metastasized melanoma
MIA (melanoma inhibitory activity)
Preoperative: 59% at stage III, 89% at stage IV

Thyroid Cancer
Thyroglobulin
Tissue-specific, glycoprotein produced by thyroid
follicular cells
Also increased in breast or lung cancer
Thyrocalcitonin
From thyroid C cells & medullary thyroid cancer
Effective to screen patients with 1st degree
relatives affected by medullary thyroid cancer and
multiple endocrine neoplasia type 2 (MEN2)

Neuroendocrine Tumors
Neuron-specific enolase (NSE)
A neuronal isoenzyme of cytoplasmic enzyme
enolase, in neuroendocrine cells
As a prognostic factor in neuroblastoma
Occurs in neuroendocrine tumors: medullary
carcinoma of the thyroid, pheochromocytoma,
carcinoid tumors; immature teratoma, small cell
carcinoma of lung, non-small-cell cancer, melanoma.
Correlate with stage and bulk of disease
N-myc oncogene in neuroblastoma N-myc copy
number is associated with stage and prognosis

Common Tumor Markers

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