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 Cancer is supposed to be the second largest killer after cardiovascular diseases throughout the globe. Breast cancer is the leader, followed by the cancer of prostate, lung, colon- rectum and bladder. No one, No age are immune. 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. 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. 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. 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 T 0 T 1 T 2 T 3 T 4 ; N 0 N 1 N 2 N 3 ; M 0 M 1 …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).