Immunohistochemical Study on Pten and Cyclin D1 in Non-Neoplastic and Neoplastic Endometrial Lesions

Abstract

Abstract
 Introduction: Endometrial carcinoma (EC) is the most common gynaecological malignancy in developed countries and has been classified into two groups, type 1 and type 2. Type 1 or endometrioid endometrial carcinomas (EECA) accounts for 80% of EC and are thought to develop following a continuum of premalignant lesions ranging from endometrial hyperplasia without atypia (EH) and atypical hyperplasia (AH). PTEN (phosphatase and tensin homolog), a tumor suppressor gene is commonly inactivated in 83 % of endometrioid carcinoma and 55% of precancerous lesions. Cyclin D1, a cell cycle regulator is overexpressed in about 40% of endometrial carcinomas.
 Aim: To study the expression of PTEN (Phosphatase and tensin homolog) and Cyclin D1 in non-neoplastic and neoplastic endometrial lesions by immunohistochemistry (IHC).
 Methods: A 2 year cross-sectional study (September 2017 to August 2019) on 115 endometrial samples was done in the Department of Pathology, RIMS. Histomorphological features and IHC expression of PTEN and Cyclin D1 in the various endometrial lesions were studied and evaluated, data collected in IBM SPSS Statistics 21 was statistically analyzed using Chi - square and Fisher’s Exact test.
 Results: Out of the 115 cases, 47(40.9%) were diagnosed as benign proliferative endometrium, 20(17.4%) benign secretory endometrium, 21(18.3%) hyperplasia without atypia, 15(13.0%) atypical hyperplasia and 12(10.4%) endometrial carcinoma with an age group spanning from 26-68 years (mean age = 46.4). Following IHC staining, 91.7%(11/12) and 83.3%(10/12) cases of EC and 80%(12/15) and 73.3%(11/15) cases of AH showed complete loss of PTEN expression and Cyclin D1 overexpression, respectively when compared to other benign lesions and was statistically significant (p < .001).
 Conclusion: Loss of PTEN and Cyclin D1 overexpression was seen in a significant number of EECA and AH, suggesting both as an early event in endometrial carcinogenesis. Therefore, we propose the use of PTEN and Cyclin D1 immunostaining as an adjunct to histopathological diagnosis as it may be informative in the identification and further management of premalignant endometrial lesions that are likely to progress to carcinoma
 Keywords: PTEN, Cyclin D1, endometrial hyperplasia, endometrial carcinoma, endometrioid endometrial carcinomas.

Expression and significance of cyclin D1, cyclin-dependent kinase 4 and cyclin-dependent kinase inhibitor P27 in patients with non-neoplastic epithelial disorders of the vulva

“…However, the upregulation of CDK4 and cyclin D, as well as the downregulation of P27, can promote cell division and proliferation disorders, and thereby induce numerous types of human tumors (for example, esophageal squamous cell carcinoma, lung cancer, oral squamous cell carcinoma, renal pelvis and ureter cancer, vulvar cancer, etc.) (17)(18)(19)(20)(21)(22)(23)(24)(25). Therefore, investigation of the expression of cyclin D1, CDK4 and P27 in patients with NNEDV is potentially of great importance.…”

“…Previous studies have confirmed that cyclin D1 and CDK4 are protooncogenes and are upregulated in numerous types of tumors (26)(27)(28)(29). One study (20) revealed that the expression levels of cyclin D1 tended to increase as vulvar tissue progressed from normal to NNEDV, vulvar intraepithelial neoplasia (VIN) and vulvar squamous cell carcinoma (SCCV), and the expression of cyclin D1 was significantly increased in vulvar carcinoma. These findings indicate that the high expression of cyclin D1 is associated with the occurrence and development of vulvar carcinoma.…”