Tumor markersx
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Transcript Tumor markersx
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).