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TUMOR MARkERS
Tumor markers are molecules occurring in blood or tissue that are associated with cancer and whose measurement or identification is useful in patient diagnosis or clinical management. The ideal marker would be a “blood test” for cancer in which a positive result would occur only in patients with malignancy, one that would correlate with stage and response to treatment and that was easily and reproducibly measured
Tumor markers can be used for one of four purposes: (1) screening a healthy population or a high risk population for the presence of cancer; (2) making a diagnosis of cancer or of a specific type of cancer; (3) determining the prognosis in a patient; (4) monitoring the course in a patient in remission or while receiving surgery, radiation, or chemotherapy.
Carcinoembryonic Antigen
The CEA was one of the first oncofetal antigens to be described and exploited clinically. It is a complex glycoprotein of molecular weight 20,000 that is associated with the plasma membrane of tumor cells, from which it may be released into the blood
Although CEA was first identified in colon cancer, an abnormal CEA blood level is specific neither for colon cancer nor for malignancy in general. Elevated CEA levels are found in a variety of cancers other than colonic, including pancreatic, gastric, lung, and breast
It is also detected in benign conditions including cirrhosis, inflammatory bowel disease, chronic lung disease, and pancreatitis. The CEA was found to be elevated in up to 19 percent of smokers and in 3 percent of a healthy control population. Thus, the test for CEA cannot substitute for a pathological diagnosis...
The CEA is of some use as a monitor in treatment
Usually the CEA returns to normal within 1 to 2 months of surgery, but if it returns elevated persistent disease may be indicated. The test is not infallible in patients treated with radiotherapy and chemotherapy but can be useful in those whose tumor is not measurable
Alpha-Fetoprotein
Alpha-Fetoprotein is a normal fetal serum protein synthesized by the liver, yolk sac, and gastrointestinal tract that shares sequence homology with albumin. It is a major component of fetal plasma, reaching a peak concentration of 3 mg/ml at 12 weeks of gestation. Following birth, it clears rapidly from the circulation, having a half life of 3.5 days, and its concentration in adult serum is less than 20 ng/ml
AFP is of importance in diagnosing hepatocellular carcinoma and may be useful in screening procedures. AFP elevation is more common in areas where hepatocellular carcinoma is endemic, such as Africa and in patients who are HBsAg positive
An elevated AFP has been termed by Sell “the single most discriminating laboratory test indicative of malignant disease now available.” As such, it could be valuable in screening for hepatocellular carcinoma in high risk populations.
The AFP is less frequently elevated in other malignancies such as pancreatic cancers, gastric cancers, colonic cancers, and bronchogenic cancers. This elevation was not necessarily associated with liver metastases
The AFP is rarely elevated in healthy persons, and a rise is seen in only a few disease states. Elevation occurs in certain liver diseases, especially acute viral or drug induced hepatitis and conditions associated with hepatic regeneration. In general, the elevations are under 500 ng/ml and do not denote hepatocellular carcinoma
Thus, AFP is a useful marker in hepatocellular carcinoma and germ cell tumors, the only conditions associated with extreme elevations greater than 500 ng/ml. In both tumors it has value in diagnosis and monitoring of therapy. In the former, which is one of the most common tumors worldwide, AFP may be of use in screening
CA 125
CA125 is an antigen present on 80 percent of nonmucinous ovarian carcinomas. It is defined by a monoclonal antibody (OC125) that was generated by immunizing laboratory mice with a cell line established from human ovarian carcinoma. It circulates in the serum of patients with ovarian carcinoma and was therefore investigated for possible use as a marker
CA125 is often elevated in patients with ovarian cancer, its level following the patient’s clinical course. With surgical resection or chemotherapy, the level correlates with patient response
The CA125 is elevated in other cancers including endometrial, pancreatic, lung, breast, and colon cancer, and in menstruation, pregnancy, endometriosis, and other gynecologic and non gynecologic conditions.
Because of the low prevalence of ovarian cancer, the test is not itself useful in screening
CA19-9
CA19-9 is a monoclonal antibody generated against a colon carcinoma cell line to detect a monosialoganglioside found in patients with gastrointestinal adenocarcinoma. It is found it to be elevated in 21 to 42 percent of cases of gastric cancer, 20 to 40 percent of colon cancer, and 71 to 93 percent of pancreatic cancer, and has been proposed to differentiate benign from malignant pancreatic disease, but this capability remains to be established
Prostate-Specific Antigen
PSA seems to have the capability of achieving at least one of the characteristics of ideal tumor marker- tissue specificity; it is found in normal prostatic epithelium and secretions but not in other tissues. It is a glycoprotein, whose function may be to lyse the seminal clot
PSA is highly sensitive for the presence of prostatic cancer. The elevation correlated with stage and tumor volume. It is predictive of recurrence and response to treatment. Finally, the antigen has prognostic value in patients with very high values prior to surgery are likely to relapse
Unfortunately, PSA is detectable in normal men and often is elevated in benign prostatic hypertrophy, which may limit its value as a screening tool for prostate cancer. A recent study has shown that PSA combined with rectal exam is a better method of detecting prostate cancer than rectal exam alone