TELOMERASE ACTIVITY IN BENIGN AND MALIGNANT EPITHELIAL OVARIAN-TUMORS

Background: Ovarian epithelial tumors include benign lesions lacking i nvasive and metastatic abilities (cystadenomas) in addition to maligna nt lesions (carcinomas). An intermediate category, called tumors of lo w malignant potential (LMP), is also recognized. The merit of this cla ssification is being challenged because the clinical behavior of LMP t umors appears closer to that of cystadenomas than to that of carcinoma s. Purpose: To verify our hypothesis that the expression of the enzyme telomerase distinguishes these two categories of ovarian epithelial t umors, we examined and compared such expression in ovarian cystadenoma s and carcinomas. By examining the expression of telomerase in LMP tum ors, we then sought to determine if these tumors were more closely rel ated to cystadenomas or to carcinomas with regard to telomerase expres sion. Methods: We examined a total of 64 consecutive ovarian tumors su bdivided into 20 carcinomas, 17 LMP tumors, and 27 cystadenomas. We su bsequently discarded three of the 27 cystadenomas because of the prese nce of admired normal ovarian stroma in those specimens. Tumor subtypi ng was done without knowledge of the telomerase results, and telomeras e assays were likewise interpreted without knowledge of tumor types. T elomerase activity was determined by use of the TRAP (i.e., telomeric repeat amplification protocol) assay. Differences between the proporti ons of tumors expressing this enzyme in each subgroup were evaluated b y use of Fisher's exact test (two-sided). Results: Telomerase activity was detected in all 20 carcinomas and in all 17 LMP tumors examined. In contrast, it was not detected in 19 of the 24 cystadenomas. These d ifferences between rates of telomerase expression in either carcinomas or LMP tumors and those in cystadenomas were statistically significan t (P<.0001). All five of the telomerase-positive cystadenomas belonged to a variant called papillary cystadenomas, whereas none of the telom erase-negative cystadenomas belonged to this variant (P<.0001). Conclu sions and Implications: The presence of telomerase expression in ovari an LMP tumors supports the merit of continuing to separate these tumor s from cystadenomas, in spite of their apparent benign clinical course . The finding of telomerase expression in papillary cystadenomas sugge sts that such tumors may be mechanistically related to LMP tumors and should perhaps be reclassified as variants of LMP tumors. Lack of telo merase expression in ovarian cystadenomas raises questions about the a lleged immortality of these tumors because expression of this enzyme i s thought to be essential for continuous growth in adult tumors.