Combining CA 125 and SMR serum markers for diagnosis and early detection of ovarian carcinoma

• Published in: Gynecologic oncology Vol. 95; no. 1; pp. 9 - 15
• Main Authors: McIntosh, M.W., Drescher, C., Karlan, B., Scholler, N., Urban, N., Hellstrom, K.E., Hellstrom, I.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2004
• Subjects: CA-125 Antigen - blood; Cancer screening; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; GPI-Linked Proteins; Humans; Longitudinal Studies; Membrane Glycoproteins - blood; Mesothelin; Ovarian Diseases - blood; Ovarian Neoplasms - blood; PEB algorithm; ROC Curve; Sensitivity and Specificity; Tumor markers; Mesothelin; SMR; MPF; Tumor markers; PEB algorithm; Cancer screening
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2004.07.039

The serum tumor marker CA 125 is elevated in most clinically advanced ovarian carcinomas. Because these elevations may precede clinical detection by a year or more, CA 125 is potentially useful for early detection as part of an ovarian cancer screening program. However, CA 125 is often not elevated in clinically detected cancer and is frequently elevated in women with benign ovarian tumors. CA 125 may be more useful in conjunction with one or more other tumor biomarkers. Additional markers could play a role if, when used with CA 125, they identify some carcinomas missed by CA 125 (i.e., they improve sensitivity), rule out false positives (i.e., improve specificity), or are able to detect the same cancers earlier.
We have evaluated a composite marker (CM) that combines CA 125 and a previously described soluble mesothelin related (SMR) marker in sera from 52 ovarian cancer cases, 43 controls with benign ovarian tumors, and 220 normal risk controls who participated in a screening program, including 25 healthy women having two serum samples collected 1 year apart. CA 125, SMR, and CM were evaluated for their ability to identify clinical disease and for their temporal stability, which assesses their ability to obtain even greater sensitivity when used in a longitudinal screening program.
CM has the best sensitivity, with specificity equal to CA 125. Importantly, CM has temporal stability at least as high as CA 125.
The CM may outperform CA 125 alone in a longitudinal screening program as well as in a diagnostic setting.