IMMUNOHISTOCHEMICAL EXPRESSION OF CYCLIN D1 IN ENDOMETRIAL CARCINOMA.

Abstract

EC is considered as one of the most common malignant tumors of the female reproductive tract. EC is most typically diagnosed after menopause, with a peak incidence of 60 to 70 years. Risk factors include obesity, nulliparity, hormonal imbalance and genetic predisposition. Molecular classification of EC includes POLE mutated type, hypermutated type with MSI instability and p53 mutant type. Prognostic factors of EC include: stage and its parameters, endometrial thickness, p53 status, MMR status.The tumor stage is determined by: Histological subtype and grade, Uterine serosal involvement, Adnexal involvement, Parametrial invasion, Myometrial invasion, Cervical stromal invasion, Vaginal involvement, Lymphovascular space invasion (LVI) andLymph node involvement. Cyclin D1 is a crucial regulator of cell cycle progression and participates in DNA synthesis. Cyclin D1 regulates the G1-S phase transition by both CDK-dependent and CDK-independent pathways. During cell cycle progression most oxidative DNA lesions occurring in the G1 phase are repaired by MMR proteins. Persistent expression of cyclin D1 during S-phase increases the mutational burden and promotes microsatellite instability due to inability of MMR proteins to bind to PCNA, persistently occupied by p21.