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Tumor markers
Definition
Cancer
Carcinogenic agents, Endocrine factors
Oncogenic viruses, and Ionizing radiation
Metastasis
Main tumor markers CEA, AFP, HCG and PSA
Definition
 Tumor markers are biochemical indicators of the
presence of tumor (cancer). They include cell
surface antigens, cytoplasmic proteins, enzymes
and hormones.
 Their main utility in clinical medicine as
laboratory test to support the diagnosis.
 Some tumor markers are also of value in
determining the response to therapy and
indicating relapse during the follow up period.
Cancer
• One of the key differences between the cancer
cells and normal cells is the inability of cancer
cells to stop dividing.
• Cancerous cells are characterized by 3 main
properties:
1) Unrestricted growth,
2) Invasion on local tissues, and
3) Spread or metastasis to other parts of the body
Cancer
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Cancer is supposed to be the second largest killer after cardiovascular diseases
throughout the globe.
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Breast cancer is the leader, followed by the cancer of prostate, lung, colonrectum and bladder.
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No one , No age are immune .
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Victims of cancer may die within a month or months or may even remain alive
for years together with help of treatment and proper care.
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Today, may carcinogens are on the list , which can produce cancer in the
humans. Carcinogens may be either exogenous or endogenous in nature.
• There are 4 groups of carcinogens :
I.
Chemical compound
II. Endocrine factors
III. Oncogenic viruses
IV. Ionizing radiations
Chemicals recognized
as carcinogens in
human
Endocrine factors
• It has been established that may hormones are responsible for
the onset of cancer.
• Examples include estrogens and androgens for premenopausal
breast and prostatic carcinoma.
• Estrogens are amongst chemical compounds whose carcinogenic
action is distant to the site of administration and limited to
specific target tissues.
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May cause:
Pituitary adenoma
Interstitial cell tumors of the testis
Carcinoma of the uterine cervix
leukaemia
Oncogenic viruses
• Oncogenes viruses have been noticed to be the agents of causation of
malignancies in human.
• They are also known as filterable viruses and belong to both DNA and RNA
virus groups.
• There are now over 100 viruses known today that play a role in the
causation of a wide spread of neoplasms in the many species.
• Among the DNA viruses are the Papova group , a name derived from
combination of Papilloma, Polyoma, and Vacuolating viruses whereas
RNA viruses are grouped under the term leuko-viruses.
• Oncogenes were first recognized as unique genes of tumor-causing viruses
that are responsible for the process of transformation (viral oncogenes)
Ionizing radiation
• Ionizing radiation are carcinogenic whether delivered from external
sources or from administered in the form of the fission products.
• Exposures to radiation resulted in an increased incidence of leukaemia
and mammary tumors.
• Radioactive fission products of plutonium causing fibrosarcomas and
osteosarcomas.
• Ultraviolet rays are also responsible for cancers of skin.
Metastasis
• In general tem metastasis is the spread of cancer cells from a
primary place of origin to other tissues where they grow as
secondary tumor.
• Many studies are being done to uncover the possible role of
certain enzymes like proteases(e.g., type 4-collagenase) and
certain other complex substances like glycoproteins and
glucosphingolipid (which remain present on the surface of
the cell) in the phenomenon of metastasis.
Metabolism of cancer cells
• Malignant cells tend to utilize anywhere from 5 to 10 times as much
glucose as normal cells and convert most of it to lactic acid, even though
they have normal rate of respiration.
• Cancerous cells exhibit the following salient features:
1) Low level of enzymes, i.e.,
A. Cytochrome oxidase.
B. Succinic dehydrogenase
C. D-amino acid oxidase
2) Raised level of enzymes, i. e.,
A. Nucleases
B. Arginase
C. Xanthine oxidase
D. β-glucuronidase
E. Certain peptidases
F. Glycolytic enzymes.
Cancer staging
• Cancer staging is the process by which cancer is divided into groups of
early and late cancer.
• Classification is useful for prognosis and helps guide clinicians in selecting
therapy and evaluating clinical outcome.
• “TNM” is currently the most widely used system to classify cancer,
replacing the historical of I to IV or A to D.
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This system described the anatomical extent of disease in 3 components:
T: the extent of the primary tumor
N: the presence or absence and extent of lymph node metastasis.
M: the presence or absence of distant metastasis.
The addition of numbers to these components indicates the extent of disease
Example T0 T1 T2 T3 T4 ; N0 N1 N2 N3 ; M0 M1 …ect
Main tumor markers
(1) Carcinoembryonic antigens (CEA)
 CEA normally is produced in embryonic tissue of the gut, pancreas and liver.
 It is a complex glycoprotein that is elaborated by many different neoplasm.
 CEA reported to be positive in 60-90% of colorectal carcinoma and 25-50% of
gastric and breast carcinoma.
 CEA elevation has also been reported in many disorders such as alcoholic
cirrhosis, hepatitis, ulcerative colitis.
 Occasionally level of CEA is elevated in apparently smokers, thus CEA lacks both
the sensitivity and specificity required for the detection of early cancer.
 In patients with CEA positive colon cancers, the presence of elevated CEA level at
6 weeks is often preceding clinically detectable disease.
 Serum CEA is also useful in monitoring the treatment of metastatic breast
cancer.
(2) Alpha-fetoprotein (AFP)
 This glycoprotein synthesized normally early in fetal life by yolk cell sac,
fetal liver and fetal gastrointestinal tract.
 In adults, the elevated level of AFP principally in liver and germ cells of
the testis.
 Elevated plasma AFP is also found less regularly in carcinoma of colon,
lung, and pancreas.
 Some non-neoplastic conditions including cirrhosis, toxic liver injury,
hepatitis and pregnancy (specially fetal distress and death).
 Marked elevation of plasma AFP is useful indicator of hepatocellular
carcinoma and germ-cell tumors of testis.
 AFP level declines rapidly after surgical resection of liver cell cancer or
treatment of germ cell tumor.
(3) Human chorionic gonadotrophin (β-HCG)
 It is 2 subunits glycopeptide hormone produced by syncytotrophoblasts
of the fetal placenta that maintains the function of corpus luteum during
the first few week of pregnancy.
 It stimulates fetal testicular secretion of testosterone .
 β-HCG is detected in urine of pregnant woman as routine common test for
pregnancy.
 β-HCG is elevated in case of trophoblastic disease (Choriocarcinoma) and
non-seminomatus germ cell tumor.
(4) Prostate specific antigen (PSA)
 Prior to introduction of testing for PSA, two-thirds of prostate cancer were
discovered after they were incurable.
 By this test, physician / surgeon can now catch most prostate cancers
before they spread beyond the prostate.
 PSA is not found normally in a healthy man blood.
 There are 2 values of PSA : benign prostatic hyperplasia(BPH) and prostate
cancer.
 PSA level under 4ng/ml considered normal.
 Above 10ng/ml biopsy is needed ( between 4 and 10ng/ml consider what
they called diagnostic gray zone).