New tumor markers: CA125 and beyond

Abstract

A variety of biomarkers have been developed to monitor growth of ovarian cancer and to detect disease at an early interval. CA125 (MUC16) has provided a useful serum tumor marker for monitoring response to chemotherapy, detecting disease recurrence, distinguishing malignant from benign pelvic masses, and potentially improving clinical trial design. A rapid fall in CA125 during chemotherapy predicts a favorable prognosis and could be used to redistribute patients on multiarmed randomized clinical trials. Several studies now document that CA125 can serve as a surrogate marker for response in phase II trials. Serial measurement of CA125 might also provide a useful marker for monitoring stabilization of disease with cytostatic targeted therapeutic agents. The greatest potential for serum markers may be in detecting ovarian cancer at an early stage. A rising CA125 can be used to trigger transvaginal sonography (TVS) in a small fraction of patients. An algorithm has been developed that calculates risk of ovarian cancer based on serial CA125 values and refers patients at highest risk for TVS. Use of the algorithm is currently being evaluated in a trial with 200,000 women in the UK that will test critically the ability of a two-stage screening strategy to improve survival in ovarian cancer. Whatever the outcome, as 20% of ovarian cancers have little or no expression of CA125, additional serum markers will be required to detect all patients in an initial phase of screening. More than 30 serum markers have been evaluated alone and in combination with CA125 by different investigators. Some of the most promising include: HE4, mesothelin, M-CSF, osteopontin, kallikrein(s), and soluble EGF receptor. Two proteomic approaches have been used: one examines the pattern of peaks on mass spectroscopy and the other uses proteomic analysis to identify a limited number of critical markers that can be assayed by more conventional methods. Both approaches are promising and require further development. Several groups are placing markers on multiplex platforms to permit simultaneous assay of multiple markers with very small volumes of serum. Mathematical techniques are being developed to analyze combinations of marker levels to improve sensitivity and specificity. In the future, serum markers should improve the sensitivity of detecting recurrent disease as well as facilitate earlier detection of ovarian cancer.

Tissue CA125 and HE4 Gene Expression Levels Offer Superior Accuracy in Discriminating Benign from Malignant Pelvic Masses

“…So far, cancer antigen 125 (CA125) is the most widely used serum biomarker for detecting and monitoring ovarian cancer in the clinical setting (Bast et al, 2005;Duffy et al, 2005;Sturgeon et al, 2008;Medeiros et al, 2009). Nevertheless, elevated serum CA125 levels are only seen in 50% of patients presented with early stage ovarian cancer and 80%-90% of patients with late stage disease, thus limiting its sensitivity (Molina et al, 1992;Rosen et al, 2005).…”

Human epididymis protein 4 (HE4) in benign and malignant diseases

“…Thus, there is a need to detect ovarian cancer when it is suffi ciently small to be curable by existing therapies (1) . Cancer antigen 125 (CA 125) in serum has a high sensitivity for ovarian cancer, but CA 125 levels are frequently elevated in women with benign gynecological diseases, resulting in a reduced specifi city of this marker, especially in premenopausal women (2,3) . Therefore, there is a need for additional markers that can complement CA 125, both for early detection and differential diagnosis.…”

Epitope presentation is an important determinant of the utility of antigens identified from protein arrays in the development of autoantibody diagnostic assays

“…complement each other and increase the specificity [11] of earlier detection a simple, blood based detection method using robust biomarkers available in the clinic is needed to assist with ovarian cancer diagnosis…”