Helpful Information about Serum Tumor Markers
Using non-invasive methods to detect early cancers, such as measuring tumor marker levels, is a commonly recognized method for cancer screening. With the exception of the prostate specific antigen (PSA), most tumor markers do not have sufficient sensitivity or specificity for use in early screening. Thus, using tumor markers alone often is not clinically useful and should be combined with other diagnostic modalities. However, they do have a crucial role for detecting disease and disease recurrence, and assessing response to tumor therapy in a selected group of patients.
Carcinoembryonic Antigen (CEA)
CEA is an onco-fetal glycoprotein expressed in normal mucosal cells and overly expressed in adenocarcinoma, especially colon cancer. Other cancers, such as lung cancer, breast cancer, and cervical cancer, may also cause increase in CEA. Non-neoplastic causes, including smoking, peptic ulcer disease, inflammatory bowel disease, cirrhosis, and biliary disease, may also be associated with elevated levels. In non-smokers, CEA should be < 5 ng/ml; if CEA is ≧10 ng/ml, one would be advised to rule out malignant cause. Because CEA cannot pinpoint tumor location or differentiate between benign and malignant diseases, it should be combined with other screening modalities, like colonoscopy. Its primary usage is to follow patients with recurrent colon cancer.
Alpha-fetoprotein (AFP)
AFP is a glycoprotein in fetal serum and drops to undetectable levels after birth. Normal AFP levels are usually <20 ng/ml and levels <200 ng/ml are often due to non-malignant causes. Primary malignancies associated with AFP elevation are hepatocellular carcinoma (HCC) and non-seminomatous germ cell tumors. Other gastrointestinal cancers, including gastric, colon, and pancreatic cancers, may cause increased levels. Non-neoplastic causes include acute, chronic hepatitis B and C, liver cirrhosis, pregnancy, and neuroblastoma.
AFP levels are abnormal in 60-80% of patients with HCC, often exceeding 1,000 ng/ml in 40% of these patients. AFP alone is not very useful for screening purposes and should be combined with an abdominal sonogram and liver function test for patients of high risks (hepatitis B chronic carriers, cirrhosis patients, chronic hepatitis B and/or C patients). if >1000ng/ml should rule out HCC.
Prostate-specific Antigen (PSA)
PSA is a glycoprotein produced by prostate epithelium. Normal serum levels are between 3.5-4.0 ng/ml. While PSA levels may normally increase with age, elevated levels may be due to prostate cancer, prostatitis, benign prostatic hypertrophy, prostatic trauma, and bladder infection. Since Taiwan’s national prostate cancer prevalence rate is generally lower, its predictive value may be lower. As such, PSA should not be the only screening tool, but should be combined with a digital exam.
Cancer Antigen 125 (CA-125)
CA-125 is a glycoprotein that lines the ovaries and is expressed by coelomic epithelium during fetal development. Elevation of CA-125 is associated with ovarian cancer, uterine cancer, and endometrial cancer. Many benign disorders, such as endometriosis, pelvic inflammatory disease, ovarian cyst, myoma, adenomyosis, and other non-gynecological causes (e.g. pancreatitis, cancer, liver cancer, hepatitis), may also be associated with elevated levels.
Due to low sensitivity and low disease prevalence, CA-125 is not very useful in early cancer screening and therefore has low positive prediction value. In post-menopausal women with a pelvic mass, if CA-125 >65µ/ml, its positive predictive value can reach 90-98% for ovarian cancer. In pre-menopausal women, CA-125 is less useful. This test should be combined with other exam methods for better screening value.