Tumor markers
Doç.Dr. Jale Çoban
Klinik Biyokimya Uzmanı
Definition
• Tumor markers are substances produced
either directly by tumor cells or by a tumorcell-induced synthesis in non-tumorous
cells.
Classification
• Onkofetal proteins
• Carcinoembryonic antigen (CEA)
• Alpha-fetoprotein (AFP)
• Human chorionic gonadotropin (hCG)
• Carbohydrate antigen
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CA-125
CA-19-9
CA-15-3 and CA 27-29
CA- 72-4
• Enzymes
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Creatin kinasa
Lactat dehidrogenasa
Prostata acid phosphatase
Prostate specific antigen (PSA)
Neuron-specific enolasa (NSE)
Amylase
• Hormones and hormone receptors
• ACTH and other endocrine hormones
• Brest estrogen and progesterone receptors
• Proteins as tumor markers
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Β2- microglobulin
C-peptid
Ferittin
Tireoglobulin
• Other markers
– Cytokeratin-19 (CYFRA 21-1)
• Tissue polypeptide-antigen (TPA)
• Tissue polypeptide-specific (TPS) antigen
• Squamous cell carcinoma (SCC) antigen
IDEAL TUMOR MARKER
• Be specific to the tumor
• Level should change in response to tumor size
• An abnormal level should be obtained in the
presence of micrometastases
• The level should not have large fluctuations that are
independent of changes in tumor size
• Levels in healthy individuals are at much lower
concentrations than those found in cancer patients
• Predict recurrences before they are clinically
detectable
• Test should be cost effective
• Criteria for ideal tumor marker, which
would have sensitivity and specificity
100% have not been fulfilled by any
known tumor marker
• Use can be helpful to diagnose the
cancer but it can not to be the only
criteria
İndication
• Early detection of malignant tumors in
high-risk groups
• Use in primary diagnosis
• Prognostic utility
• Therapy monitoring
• Early detection on tumor recurrence
COMMON TUMOR MARKERS
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CEA - Monitor colorectal, breast, lung cancer
CA-125 - Ovarian cancer monitoring
CA15-3 - Monitor recurrences of breast cancer
AFP - Germ cell tumors, liver cancer
Total PSA - Screen and monitor prostate cancer
Free PSA - Distinguish prostate cancer from BPH
HCG - Germ cell and trophoblastic tumors
Hormone receptors - Breast cancer therapy
NMP 22 - Monitor recurrences of bladder cancer
Tumor markers are not suited for
screening asymptomatic individuals
because they have a too low organ and
tumor specificity as well as a too low
predictive value positive of a test
AFP
(alpha – fetoprotein)
• The most widely used biochemical blood
test for liver cancer - hepatocellular
carcinoma (HCC) is alpha-fetoprotein (AFP)
• AFP is a protein normally made by the
immature liver cells in the fetus.
AFP
(alpha – fetoprotein)
• Malignant Conditions
1.Liver cancer - hepatocellular carcinoma
2. Germ cell tumors
(cancer of the testes and ovaries)
3. Metastatic cancer in the liver
(originating in other organs)
• Non-Malignant Conditions
Pregnancy
Cirrhosis
Hepatitis
Absolute indication
• Suspected hepatocellular carcinoma
• Germ cell tumors (testes, ovaries,
extragonadal tumors)
• Follow-up of patients after treatment for
germ cell tumors or primary liver cell
cancers or of those still undergoing
treatment, e.g. Postoperatively or
during/after irradiation and chemotherapy
Relative indications
• Monitoring patients liver cirrhosis for the
development of primary liver cell cancer
• Monitoring patients who are at increased risk for
germ cell tumors , e.g. cryptorchidism and
healthy monozygotic twin siblings of patients
with a testicular tumor.
• Monitoring patients following resection of a
testicular tumor who are in complete remission,
because of the increased risk of developing a
second, contralateral tumor.
Cirrhosis
(AFP)
Hepatocellular carcinoma
Germ cell tumors
(Testis Tm)
CEA
(carcinoembryonic antigen)
• Described by Gold and Freedman in1965
as a marker for Colorectal Cancer
• Glycoprotein with a carbohydrate
composition ranging from 50 - 85% of
molecular mass
• It is normally produced during fetal
development, but the production of CEA
stops before birth.
• CEA levels are raised in heavy smokers
CEA
(carcinoembryonic antigen)
• CEA levels 5 - 10 times upper limit of
normal suggests colon cancer
• Differential diagnosis of liver tumors
• CEA is not used to screen for colon cancer
Increased levels of CEA
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Colorectal carcinoma
Pancreatic carcinoma
Lung carcinoma
Breast carcinoma
CEA Distribution In Patients
With Malignant Disease
% Distribution of CEA
Colorectal
0-3
ng/ml
28
3.1 – 10
ng/ml
20
>10
ng/ml
52
Breast
50
27
23
Ovarian
80
16
4
Pulmonary 39
29
32
colorectal carcinomas
colorectal carcinomas
(CEA)
HCG
(HumanChorionic Gonadotropin)
• Absolute indications
1. Germ cell tumors (cancer of the
testes and ovaries) – hydatiform mole and
choriocarcinoma in women , testicular
cacer in men
2. Extragonadal germ tumors
Germ cell tumors
(Testis Tm)
CA 19-9
Suspected presence of
• pancreatic,
• hepatobiliary (liver cancer, biliary cancer),
or
• gastric cancer
• Diagnosis and monitoring of colorectal
cancer( second-line tumor marker after
CEA) and ovarian cancer (second-line
tumor marker after CA125)
Pancreatic Cancer
Pancreatic Cancer
Pancreatic Cancer
Pancreatic Cancer
Pancreatic Cancer
CA 125
• CA-125 glycoprotein molecular weight 2001,000 kda
• Introduced in 1983 by Bast for ovarian cancer
• Cut-off: 35 U/ml
• The major diagnostic relevance of CA 125 is in
assisting the diagnosis of ovarian cancer,
evaluating the success of treatment, and the
disease course.
• Furthermore, it may be used as a second-line
marker, after CA19-9, for pancreatic cancer.
CA-125 Distribution In Patients With
Malignant Disease
% Distribution of CA-125
Cancers
<35 U/ml
35-65 U/ml
>65 U/ml
Ovarian
14
9
77
Lung
56
19
25
Breast
82
8
10
Endometrial 70
8
22
Cervical
66
15
19
Colorectal
76
11
12
Over Ca
Pancreas Ca
Over Ca
Over Ca
Over Ca
CA 15-3
• CA 15-3 is a useful parameter for
monitoring the disease course of patients
with metastatic breast cancer.
Breast Cancer
Breast Cancer
Breast Cancer
Breast Cancer
Breast Cancer
Metastatik meme Ca
NSE (neuron specific enolase)
• NSE is useful for monitoring the outcome
of treatment and disease course in
patients with neuroendocrine tumors, in
particular small cell lung cancer and
neuroblastoma.
PSA (prostate-spesific antigen)
• Screening of asymptomatic men > 50
years of age for the presence of prostate
cancer, together with digital rectal
examination and transrectal ultrasound
examination/biopsy on the individual
findings
Prostate cancer
Prostate cancer
?
METASTATİK KOLON CA
NÜKS OVER CA
?
OVER CA
METASTATİK MEME KANSERİ
?
?
PSA
Prostate-specific antigen
• PSA is a protein produced by the cells of the
prostate gland.
• PSA is present in small quantities in the serum
of normal men, and is often elevated in the
presence of
prostate cancer
and
in other prostate disorders
prostatitis (inflammation of the prostate) and
benign prostatic hyperplasia (BPH)