Analysis of telomerase activity in ovarian cystadenomas, low-malignant-potential tumors, and invasive carcinomas

Objective. Inappropriate telomerase expression has been reported to be asso ciated with the development and/or progression of malignancies, Therefore, the purpose of the study was to determine and evaluate the levels of telome rase activity in normal ovary, cystadenomas, low-malignant-potential tumors , and carcinomas of the ovary. Methods. In the present study, telomerase activity was examined in frozen t issue specimens of normal ovary (n = 6), ovarian cystadenomas (n = 13), ova rian low-malignant-potential (LMP) tumors (n = 12), and ovarian invasive ca rcinomas (n = 81). Clinicopathological information including age at diagnos is, histological grade, FIGO stage, presence of distant metastasis at diagn osis, and residual disease was available for all patients with ovarian carc inomas (n = 81). Telomerase activity was assessed by the telomeric repeat a mplification protocol (TRAP). Arbitrary values were assigned to processivit y of telomerase activities based on the molecular weights of the telomeric repeat DNA ladders, and were graded as "negative," "moderate" (less than or equal to 99 bp), or "high" (>100 bp) activities. The specificity of telome rase activity was determined by the pretreatment of telomerase-positive con trol or tumor samples with RNase that led to the abolition of the activity. In addition, to determine the possibility of false negativity due to the p resence of telomerase inhibitors, TRAP assay was performed on each of the t elomerase-negative specimens by mixing them individually with the telomeras e-positive control. Results. Telomerase activity in the progression of ovarian carcinogenesis w as evaluated. In comparison with normal ovary/cystadenoma (32%), a much hig her frequency of the moderate activity was observed in LMP tumors (67%) or invasive carcinomas (57%), suggesting a close association between the latte r two categories. The results reflect a subpopulation of telomerase-positiv e LMP tumor cells with the potential to develop invasive carcinomas. None o f the specimens of the benign or LIMP tumors exhibited high activity. In co ntrast, 18% of ovarian invasive carcinomas showed high telomerase activity (P = 0.013, Fisher exact test) and further 57%, moderate activity (75% in a ll). A statistically significant difference was observed in the expression of telomerase activity between normal ovary/benign cystadenomas and ovarian invasive carcinomas (P = 0.001, chi(2) test). Conclusions. The study showed a high prevalence of telomerase activity in L MP tumors or invasive carcinomas, the high levels of telomerase activity be ing associated exclusively with the invasive ovarian carcinomas, Therefore, the levels of processivity of telomerase activity and evidence of its stat istically significant association with ovarian carcinoma suggest its role i n the progression of ovarian carcinogenesis. (C) 1999 Academic Press.