Tumor-associated antigens Tumor Antigens Many tumor cells produce antigens, which may be released in the bloodstream or remain on the cell surface. Any molecule capable of being recognized by the immune system is considered an antigen... read more (TAAs) can help diagnose various tumors and sometimes determine the response to therapy or recurrence. An ideal tumor marker would
Be released only from tumor tissue
Be specific for a given tumor type
Be detectable at low levels of tumor cell burden
Have a direct relationship to the tumor cell burden
Be present in all patients with the tumor
Although most tumors release detectable antigenic macromolecules into the circulation, no tumor marker has all the requisite characteristics to provide enough specificity or sensitivity to be used in early diagnosis or mass cancer screening programs.
Carcinoembryonic antigen (CEA) is a protein-polysaccharide complex present in colon cancers and in normal fetal intestine, pancreas, and liver. Blood levels are elevated in patients with colon cancer Colorectal Cancer Colorectal cancer is extremely common. Symptoms include blood in the stool and change in bowel habits. Diagnosis is by colonoscopy. Treatment is surgical resection and chemotherapy for nodal... read more , but the specificity is relatively low because positive results also occur in people with a history of ≥ 20 pack-years of cigarette smoking and in patients with cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic fibrosis that has resulted in widespread distortion of normal hepatic architecture. Cirrhosis is characterized by regenerative nodules surrounded by dense... read more , ulcerative colitis Ulcerative Colitis Ulcerative colitis is a chronic inflammatory and ulcerative disease arising in the colonic mucosa, characterized most often by bloody diarrhea. Extraintestinal symptoms, particularly arthritis... read more , or other cancers (eg, breast Breast Cancer Breast cancers are most often epithelial tumors involving the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more , pancreas Pancreatic Cancer Pancreatic cancer, primarily ductal adenocarcinoma, accounts for an estimated 64,050 cases and 50,550 deaths in the United States annually ( 1). Symptoms include weight loss, abdominal pain... read more , bladder Bladder Cancer Bladder cancer is usually transitional cell (urothelial) carcinoma. Patients usually present with hematuria (most commonly) or irritative voiding symptoms such as frequency and/or urgency; later... read more , ovary Ovarian, Fallopian Tube, and Peritoneal Cancer Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more , cervix Cervical Cancer Cervical cancer is usually squamous cell carcinoma; adenocarcinoma is less common. The cause of most cervical cancers is human papillomavirus (HPV) infection. Cervical neoplasia is often asymptomatic... read more ). Monitoring CEA levels may be useful for detecting cancer recurrence after tumor excision if the patient initially had an elevated CEA and for refining estimates of prognosis by stage.
Alpha-fetoprotein, a normal product of fetal liver cells, is also present in the sera of patients with primary hepatocellular cancer Hepatocellular Carcinoma Hepatocellular carcinoma (HCC) usually occurs in patients with cirrhosis and is common in areas where infection with hepatitis B and C viruses is prevalent. Symptoms and signs are usually nonspecific... read more , nonseminomatous germ cell tumors, and, frequently, ovarian or testicular embryonal cancer. Levels are sometimes useful for estimating prognosis or, less often, for diagnosis.
Beta subunit of human chorionic gonadotropin (beta-hCG), measured by immunoassay, is the major clinical marker in women with gestational trophoblastic neoplasia Gestational Trophoblastic Disease Gestational trophoblastic disease is proliferation of trophoblastic tissue in pregnant or recently pregnant women. Manifestations may include excessive uterine enlargement, vomiting, vaginal... read more (GTN)—a disease spectrum that includes hydatidiform mole, nonmetastatic GTN, and metastatic GTN—and in about two thirds of men with testicular embryonal cancer or choriocarcinoma. The beta subunit is measured because it is specific for hCG. This marker is present in low levels in healthy people. Levels are elevated during pregnancy.
Prostate-specific antigen (PSA), a glycoprotein located in ductal epithelial cells of the prostate gland, can be detected in low concentrations in the sera of healthy men. Using an appropriate upper limit of normal, assays with monoclonal antibodies detect elevated serum levels of PSA in about 90% of patients with advanced prostate cancer Prostate Cancer Prostate cancer is usually adenocarcinoma. Symptoms are typically absent until tumor growth causes hematuria and/or obstruction with pain. Diagnosis is suggested by digital rectal examination... read more , even in the absence of defined metastatic disease. It is more sensitive than prostatic acid phosphatase. However, because PSA is elevated in other conditions (eg, benign prostatic hyperplasia, prostatitis, recent genitourinary tract instrumentation), it is less specific. PSA can be used to monitor recurrence after prostate cancer has been diagnosed and treated.
CA 125 is clinically useful for diagnosing and monitoring therapy for ovarian cancer Ovarian, Fallopian Tube, and Peritoneal Cancer Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more , although any peritoneal inflammatory process and some other cancers can increase levels.
Beta-2 microglobulin is often elevated in multiple myeloma Multiple Myeloma Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones that cause... read more and in some lymphomas. Its primary use is in prognosis.
CA 19-9 was originally developed to detect colorectal cancer but proved more sensitive for pancreatic cancer Pancreatic Cancer Pancreatic cancer, primarily ductal adenocarcinoma, accounts for an estimated 64,050 cases and 50,550 deaths in the United States annually ( 1). Symptoms include weight loss, abdominal pain... read more . It is primarily used to judge the response to treatment in patients with advanced pancreatic cancers. CA 19-9 can also be elevated in other gastrointestinal cancers, particularly cancer of the bile ducts, and some benign bile duct and cholestatic disorders.
CA 15-3 and CA 27-29 are elevated in most patients with metastatic breast cancer Breast Cancer Breast cancers are most often epithelial tumors involving the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more . Levels may also be elevated in other conditions. These markers are primarily used to monitor the response to therapy.
Chromogranin A is used as a marker for carcinoid Overview of Carcinoid Tumors Carcinoid tumors develop from neuroendocrine cells in the gastrointestinal tract (90%), pancreas, pulmonary bronchi, and rarely the genitourinary tract. More than 95% of all gastrointestinal... read more and other neuroendocrine tumors. Sensitivity and specificity for neuroendocrine tumors can exceed 75%, and diagnostic accuracy is higher with diffuse than with localized tumors. Levels can be elevated in other cancers, such as lung and prostate, and some benign disorders (eg, primary hypertension, chronic kidney disease, chronic atrophic gastritis).
Thyroglobulin is produced by the thyroid and may be elevated in various thyroid disorders. It is primarily used as a marker after complete thyroidectomy to detect recurrent thyroid cancer Thyroid Cancers There are 4 general types of thyroid cancer. Most thyroid cancers manifest as asymptomatic nodules. Rarely, lymph node, lung, or bone metastases cause the presenting symptoms of small thyroid... read more and to monitor the response to treatment in metastatic thyroid cancer.
TA-90 is a highly immunogenic subunit of a urinary tumor–associated antigen that is present in 70% of melanomas; soft-tissue sarcomas; and cancers of the breast, colon, and lung. Some studies have shown that TA-90 levels can accurately predict survival and the presence of subclinical disease after surgery for melanoma (1, 2 General references Tumor-associated antigens (TAAs) can help diagnose various tumors and sometimes determine the response to therapy or recurrence. An ideal tumor marker would Be released only from tumor tissue... read more ).
1. Kelley MC, Jones RC, Gupta RK, et al: Tumor-associated antigen TA-90 immune complex assay predicts subclinical metastasis and survival for patients with early stage melanoma. Cancer 83(7):1355-1361, 1998. doi:10.1002/(sici)1097-0142(19981001)83:7<1355::aid-cncr12>3.0.co;2-3
2. Kelley MC, Gupta RK, Hsueh EC, et al: Tumor-associated antigen TA90 immune complex assay predicts recurrence and survival after surgical treatment of stage I-III melanoma. J Clin Oncol 19(4):1176-1182, 2001. doi:10.1200/JCO.2001.19.4.1176