Immunohistochemical Detection of Human Telomerase Reverse Transcriptase (hTERT), Topoisomerase II?? Expression, and Apoptosis in Endometrial Adenocarcinoma and Atypical Hyperplasia

Abstract

This study evaluated the immunohistochemical expression of human telomerase reverse transcriptase (hTERT) in endometrial carcinoma and atypical endometrial hyperplasia, and related it to the expression of topoisomerase (TP)IIalpha (a proliferation associated enzyme); apoptosis as determined by the frequency of apoptotic bodies (ABI); mitotic counts; and other clinicopathologic variables. Immunoreactivity for hTERT and TPIIalpha as well as ABI were assessed in 57 endometrial samples (12 atypical hyperplasias, 33 endometrioid carcinomas, 12 serous/clear cell carcinomas). hTERT immunoreactivity, TPIIalpha labeling indices (LI), ABI, and ratios of the indices (ABI/TPIIalpha LI) increased from atypical hyperplasias to endometrioid carcinomas to serous/clear cell carcinomas (p < 0.0001 for each variable). hTERT expression increased with ABI (p < 0.0001), TPIIalpha LI (p = 0.0019), ABI/TPIIalpha ratios (p < 0.0001), and grade (p = 0.0005), but not with FIGO stage (p = 0.2775). TPIIalpha LI, ABI, and ratios were related to high grade (p = 0.0001 for each variable), but not with FIGO stage (p = 0.7362, p = 0.7554, and p = 0.7405, respectively). TPIIalpha LI and ABI were significantly correlated in atypical hyperplasias (p = 0.0004), endometrioid carcinomas (p < 0.0001), and serous/clear cell carcinomas (p = 0.024). Immunostaining levels for hTERT were similar in atypical hyperplasias and grade 1 endometrioid carcinomas (p = 0.1956). These results suggest that hTERT expression is closely related to proliferation, apoptosis, and high grade in endometrial carcinomas, reflecting cell cycle deregulation in endometrial carcinogenesis.

The Status of Telomerase Enzyme Activity in Benign and Malignant Gynaecologic Pathologies

“…Telomerase activity was determined to be between 14.2% and 80% in premalignant endometrial tissue samples, and the positivity rate was generally higher in lesions with cellular atypia (15,17). There was no premalignant endometrial sample in this study, but the results of a study conducted among the Turkish population were parallel with current literature published in the English language (18).…”

“…In this study, all six malignant endometrial tissue samples (100%) were found to be positive for hTERT. The positivity rate of telomerase activity in endometrioid adenocarcinoma was reported to be between 70% and 100% in previous studies (15,17,18).…”

Tubal metaplasia of the endometrium with cytologic atypia: analysis of p53, Ki-67, TERT, and long-term follow-up

“…Previous studies have shown significant overexpression of p53, Ki-67, and human telomerase reverse transcriptase (TERT) in invasive and non-invasive uterine serous carcinoma. [5][6][7][8] The current study evaluates the expression of p53, Ki-67, and TERT in atypical tubal metaplasia, and the usage of these immunohistochemical markers in differentiating this metaplasia from intraepithelial or invasive uterine serous carcinoma. This study also uses long-term follow-up to evaluate the risk of subsequent endometrial neoplasia associated with atypical tubal metaplasia.…”

Evaluation of Topoisomerase IIa Expression in Pancreatic Ductal Adenocarcinoma: A Pilot Study Using Chromogenic in situ Hybridization and Immunohistochemistry on Tissue Microarrays

“…Topo IIa, with a molecular mass of 170 kDa, is expressed in proliferating cells in the late S phase with a peak in G2-M phases [9] . Inhibition of topoisomerases promotes cell death and for this reason they are targets for specific chemotherapy [10][11][12] . Topo IIa inhibitors, such as anthracyclines, are used as adjuvant chemotherapy combined with other agents (gemcitabine) in PDAC [13,14] .…”