Clinical Profiles of Telemerase Activety in Uterine Cervical Carcinoma

Cho, Sam Hyun; Yoo, Joong Bae; Kim, Seung Ryong; Kim, Kee Sung; Ra, Myung Jae; Kim, Kyung Tai; Moon, Hyung; Hwang, Youn Yeung

Abstract

A current hypothesis gaining prominence proposes that activation of the telomerase is necessarey for cells to become immortal, or be capable of proliferating indefinitely. The theory suggersts that that almost all cancer cells must attain immortality for progression to malingnant state and, hence, require activation of telomerase. To assess the role of telomerase in the development of mailignant transformation of the uterine cervical carcinoma, telomerase activeiy was measured by using a recently developed sensitive RPR-based telomerase assay(telomeric repeat amplification protocol; TRAP)in benign uterine condition and invasive uterine cervical carcinoma tissues revealed to be telomerase positive (14/16, 88%) which represents a characteristic 6 bp ladder pattern, while none of the 4 cervical tissues with the nonspecific pathologic findings or just chronic cervictis which were obtained by simple bysterenctomy under the diagnoses of benign myoma or uterine prolapse showed any telomerase actiovity. These findings suggest that this enzyme activity may play a key role in the establishment and progression of the uterine cervical carcinoma. This activity of telomerase may influence from the initial stage of tumorigenesis of uterine cervical carcinoma because poitive findings were noticed from the early stage (stage Ia1) to the advanced stage. The results of neoadjuvant chemotherpy which were revealed in final histopathologic specimens following radical hysterectomuy, pelvic and raraaortic lymph nodes dissection (suggestion by Rosen et al,) were one grade IV wiht telomerase poistive, 2 grade III with all positivie, 5grade II with 3 positive 2 negative. The two cases of pelvic lymph node metastasis belong to the group of grade II and their activeities of telomerase were 1 positive and 1negative. The situation of apoptosis induced by antineoplastic chemotherapy has not been related to that of telomerase activeity. Furthemore, the late recurrences has been noticed over 5years follow-up following neoadjuvant chemotherapy and radical surgery for the management of the high risk group of patients (not shown in this study) This measn that the nowday's regimen for induction tumoricidals may have been operating as dual effects (partial restoring and redamaging) to the cell cycle chekpoint. Therefore if telomerase inhibitor will be applied combined whit the induction chemotherapy, unexpected benefits mignt be obtained for the patient with the advanced uterine cervical carcinoma.