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

Objective. Inappropriate telomerase expression has been reported to be associated with the development and/or progression of malignancies, Therefore, the purpose of the study was to determine and evaluate the levels of telomerase 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 tissue specimens of normal ovary (n = 6), ovarian cystadenomas (n = 13), ovarian low-malignant-potential (LMP) tumors (n = 12), and ovarian invasive carcinomas (n = 81). Clinicopathological information including age at diagnosis, histological grade, FIGO stage, presence of distant metastasis at diagnosis, and residual disease was available for all patients with ovarian carcinomas (n = 81). Telomerase activity was assessed by the telomeric repeat amplification protocol (TRAP). Arbitrary values were assigned to processivity 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 telomerase activity was determined by the pretreatment of telomerase-positive control 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 presence of telomerase inhibitors, TRAP assay was performed on each of the telomerase-negative specimens by mixing them individually with the telomerase-positive control. Results. Telomerase activity in the progression of ovarian carcinogenesis was evaluated. In comparison with normal ovary/cystadenoma (32%), a much higher frequency of the moderate activity was observed in LMP tumors (67%) or invasive carcinomas (57%), suggesting a close association between the latter two categories. The results reflect a subpopulation of telomerase-positive LMP tumor cells with the potential to develop invasive carcinomas. None of the specimens of the benign or LIMP tumors exhibited high activity. In contrast, 18% of ovarian invasive carcinomas showed high telomerase activity (P = 0.013, Fisher exact test) and further 57%, moderate activity (75% in all). 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 LMP tumors or invasive carcinomas, the high levels of telomerase activity being associated exclusively with the invasive ovarian carcinomas, Therefore, the levels of processivity of telomerase activity and evidence of its statistically significant association with ovarian carcinoma suggest its role in the progression of ovarian carcinogenesis. (C) 1999 Academic Press.