Expression of Apoptosis Related Proteins, P-Cadherin and Claudin-3 in Different Endometrial Lesions

Objective: Endometrial adenocarcinomas are the eighth leading cause of cancer deaths in women in developed countries, with several well-established prognostic factors. This study aimed to evaluate the expression of apoptosis related proteins (survivin, PTEN and Fas) as well as P-cadherin and claudin-3 in normal, hyperplastic and endometrial carcinoma to investigate their role in endometrial carcinogenesis and to explore their correlations with clinico-pathological parameters of endometrial cancer.Material and Methods: Forty paraffin embedded tissues of endometrial carcinoma and 15 of endometrial hyperplasia (4 simple, 3 complex and 8 atypical) were studied using immunohistochemistry with antibodies against survivin, PTEN, Fas, P-cadherin and claudin-3.Results: The expression of apoptosis related proteins (survivin and Fas) as well as P-cadherin and claudin-3 increased progressively from normal proliferative endometrium to atypical hyperplasia to endometrioid endometrial carcinoma (EECA) (p 0.05). PTEN expression in cyclical endometrium and non atypical hyperplasia was higher than in atypical endometrial hyperplasia (ACH) and EECA (p 0.05). Survivin, Fas, claudin-3 and p-cadherin expression was significantly correlated with myometrial invasion (p 0.05). Fas and P-cadherin expression was significantly correlated with FIGO grade (p 0.01). Survivin, Fas and P-cadherin expression was significantly correlated with FIGO stage (p 0.05).Conclusions: Lack of PTEN expression may be the earliest event in endometrial carcinogenesis. Survivin may reflect an important mechanism in tumor progression of the endometrial mucosa. Fas-related apoptotic pathway is also involved in the regulation of apoptosis in the endometrial tissue and promotes the development and progression of endometrial neoplasia. Overexpression of P-cadherin is involved in endometrial carcinogenesis and is associated with aggressive subgroups. The expression data of claudin-3 in different premalignant and malignant endometrial alterations suggest that these proteins might serve as diagnostic and prognostic marker.