What is the role of tumor markers in the diagnosis of ovarian cancer?

Updated: Aug 10, 2020
  • Author: Andrew E Green, MD; Chief Editor: Yukio Sonoda, MD  more...
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Tumor markers are glycoproteins that are usually detected by monoclonal antibodies. Each tumor marker has a variable profile of usefulness for screening, determining diagnosis and prognosis, assessing response to therapy, and monitoring for cancer recurrence. They are produced by tumor cells in response to cancer or certain benign conditions and indicate biological changes that signal the existence of malignancy. These soluble molecules can usually be detected in elevated quantities in the blood, urine, or body tissues of patients with certain types of cancer.

The levels of tumor marker are not altered in all cancer patients, especially in early-stage cancer. The level of some tumor markers can be elevated in patients with noncancerous conditions. Following the development of monoclonal antibodies, many new tumor markers have been discovered during the past 2 decades. Some tumor markers can be used for screening, diagnosis, management, determining response, and recurrence. Some markers show promise as prognostic indicators.

Due to the location of ovarian tumors within the abdominal cavity, making a preoperative pathological diagnosis of cancer is difficult without laparotomy. From this point of view, the use of tumor markers that consist of carbohydrate antigens, such as CA-125, in addition to diagnostic imaging, is useful in the diagnosis of ovarian cancer.

CA-125 is a glycoprotein antigen detected by using mouse monoclonal antibody OC125 raised from an ovarian cancer cell line. CA-125 is not specific for epithelial ovarian cancer and is elevated in other benign and malignant conditions, including menstruation; endometriosis; pelvic inflammation; liver, renal, and lung disease; and cancer of the endometrium, breast, colon, pancreas, lung, stomach, and liver. It is also elevated in 6% of women who do not have epithelial ovarian cancer. Although CA-125 is elevated in 83% of women with epithelial ovarian cancer, it is elevated in only 50% of those with stage I disease.

A monoclonal antibody-based immunoassay for CA-125 has been used to monitor the treatment of epithelial ovarian carcinomas. Persistent elevation of CA-125 in serum has generally reflected persistence of disease at second-look surveillance procedures. However, CA-125 levels can return to within normal limits and residual disease can be found at laparoscopy or laparotomy.

CA-125 is not useful when used alone as a single one-time test for ovarian cancer screening, but it may have increased value when serial measurements are performed over time and if it is incorporated into a risk of ovarian cancer algorithm. CA-125 shows promise for distinguishing benign from malignant pelvic masses. Several trials are ongoing to determine the potential of CA125 in combination with other markers to increase earlier detection of occult ovarian cancer. [39]

A study by Hirai et al found that stage IA ovarian cancers in women with normal CA125 levels are usually smaller, have slightly different histopathologic type distribution, and have less solid components than cancers with elevated CA-125 levels. [52]

A study by Buys et al found that among women in the general US population, screening simultaneously with CA-125 and transvaginal ultrasonography did not reduce ovarian cancer mortality compared with usual care. False-positive results occurred in 9.6% of women, resulting in 6.2% undergoing surgery. [53]

Tests that use multiple markers have been devised. The OVA1 test includes five markers: transthyretin, apolipoprotein A1, transferrin, beta-2 macroglobulin, and CA-125. The Ovasure test includes six markers: leptin, prolactin, osteopontin, insulinlike growth factor II, macrophage inhibitory factor, and CA-125. The National Comprehensive Cancer Network (NCCN) does not endorse either of those for ovarian cancer screening. [45]

Other markers that have been investigated include lysophosphatidic acid, tumor-associated glycoprotein 72 (TAG 72), OVX1, and macrophage colony-stimulating factor (M-CSF). Newer experimental markers have been identified through various laboratory techniques. These markers include mesothelin, human epididymis protein 4, kallikrein, and haptoglobin-alpha. A study by No et al found that p-4EBP1 expression was associated with poor prognostic factors and that overexpression may be a prognostic biomarker. [54] Tapia et al report that p-trkA may be a potential new tumor marker and that nerve growth factor may act as a direct angiogenic factor. [55]

A study by Lin et al found that the adjusted hazard ratio for ovarian cancer in women with pelvic inflammatory disorder was 1.92. This suggests that pelvic inflammatory disorder may be a useful marker for ovarian cancer. [56]

No marker is completely specific; therefore, diagnostic immunohistochemistry testing must be used in conjunction with morphologic and clinical findings.

Please go to the main article on Gynecologic Tumor Markers for more information.

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