Potential markers that complement expression of CA125 in epithelial ovarian cancer

Background. When ovarian carcinoma is diagnosed in stage 1, LIP to 90% of patients call be cured with Surgery and currently available chemotherapy. At present, less than 25% of cases are diagnosed at this stage. To increase the fraction of ovarian cancers detected at an early stage, screening strategies have been devised that utilize a rising serum CA 125 level to trigger the performance of transvaginal sonography. One limitation of CA125 as an initial step in such a screening strategy is that LIP to 20% of ovarian cancers lack expression of the antigen. Serum tumor markers that call be detected in ovarian cancers that lack CA 125 expression might improve the sensitivity for early detection. Methods. From 296 ovarian cancers, 65 (22%) were found to have weak or absent CA 125 expression oil immunoperoxidase staining. Tissue expression of CA 125 was compared to serum CA 125 levels. Using immunoperoxidase staining of tissue arrays, we have assessed expression of 10 potential serum tumor markers in file 65 epithelial ovarian cancers with little or no CA 125 expression and ill ovarian cystadenomas, tumors of low malignant potential, normal ovaries, and 16 other normal tissues. Results. Low or absent expression of CA 125 in surgical specimens of epithelial ovarian cancer was associated with low levels of serum CA 125 in pre-operative serum specimens. In ovarian cancers that lacked CA 125, all specimens (100%) expressed human kallikrein 10 (HK10), human kallikrein 6(HK6), osteopontin (OPN), and claudin 3. A smaller fraction of CA 125-deficient ovarian cancers expressed DF3 (95%), vascular-endothelial growth factor(VEGF) (81%), MUCI (62%), mesothelin (MES) (34%), HE4 (32%), and CA19-9 (29%). When reactivity with normal tissues was considered, however, MES and HE4 showed the greatest specificity. Differential expression was also found for HK10, OPN, DF3, and MUCI. Conclusions. At the level of tissue expression, each of 10 potential Set-Urn Markers could be detected in 29- 100% of ovarian cancers that had low or absent expression of CA125. Several markers exhibited more intense expression in cancers than in normal organs. Further investigation is needed to demonstrate complementary expression of markers in serum. (c) 2005 Published by Elsevier Inc.