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Tumor Immunodiagnosis

By

Dmitry Gabrilovich

, MD, PhD, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania

Last full review/revision Nov 2020| Content last modified Nov 2020
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  • 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 carcinomas and in normal fetal intestine, pancreas, and liver. Blood levels are elevated in patients with colon carcinoma Colorectal Cancer Colorectal cancer is extremely common. Symptoms include blood in the stool and change in bowel habits. Screening using one of several methods is recommended for appropriate populations. Diagnosis... read more Colorectal Cancer , but the specificity is relatively low because positive results also occur in heavy cigarette smokers 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 Ulcerative Colitis , and other cancers (eg, breast Breast Cancer Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more Breast Cancer , pancreas Pancreatic Cancer Pancreatic cancer, primarily ductal adenocarcinoma, accounts for an estimated 57,600 cases and 47,050 deaths in the US annually (1). Symptoms include weight loss, abdominal pain, and jaundice... 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 Bladder Cancer , ovary Ovarian Cancer Ovarian cancer is often fatal because it is usually advanced when diagnosed. Symptoms are usually absent in early stages and nonspecific in advanced stages. Evaluation usually includes ultrasonography... read more , cervix Cervical Cancer Cervical cancer is usually a squamous cell carcinoma caused by human papillomavirus infection; less often, it is an adenocarcinoma. Cervical neoplasia is asymptomatic; the first symptom of early... read more Cervical Cancer ). 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 carcinoma Hepatocellular Carcinoma Hepatocellular carcinoma 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 carcinoma. 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 Gestational Trophoblastic Disease (GTN)—a disease spectrum that includes hydatidiform mole, nonmetastatic GTN, and metastatic GTN—and in about two thirds of men with testicular embryonal carcinoma 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 hypertrophy, prostatitis, recent GU tract instrumentation), it is less specific. PSA can be used to monitor recurrence after prostatic carcinoma has been diagnosed and treated.

CA 125 is clinically useful for screening, diagnosing, and monitoring therapy for ovarian cancer Ovarian Cancer Ovarian cancer is often fatal because it is usually advanced when diagnosed. Symptoms are usually absent in early stages and nonspecific in advanced stages. Evaluation usually includes ultrasonography... read more , although any peritoneal inflammatory process and some other cancers can increase levels.

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 57,600 cases and 47,050 deaths in the US annually (1). Symptoms include weight loss, abdominal pain, and jaundice... 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 GI 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 cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more Breast Cancer . 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 carcinomas 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.

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