Study of prognostic and diagnostic significance of P53 and PTEN mutation in proliferative lesions of endometrium.

Background: Endometrial hyperplasia essentially implies an overgrowth of the endometrium. Complex hyperplasia associated with cellular atypia, seems to be the most important predictor of malignant potential. Endometrioid Endometrial Carcinomas account for three-fourths of Endometrial Carcinomas and are thought to develop following a continuum of premalignant lesions ranging from endometrial hyperplasia without atypia, to hyperplasia with atypia, and finally to well-differentiated carcinoma. Currently the most frequently observed gene mutation in endometrioid carcinoma is located on chromosome 10 and is related with the PTEN gene (phoshatase and tensin homolog). PTEN inactivation is found to correlate with clonal growth pattern detected in endometrial hyperplasia and carcinoma. The p53 tumor suppressor gene locates to chromosome 17p13. The abnormal p53 expression has been found in 11% of grade 1 endometrioid endometrial carcinoma, while p53 mutations occur in 90% of non-endometrioid endometrial carcinoma. Aims and objectives: In this study we aim to evaluate the immuno histochemical expression of P53 and PTEN genes in endometrial hyperplasia and endometrial carcinoma and correlate their expression with prognostic outcomes like grade and stage, in cases of endometrial carcinoma. Material and methods: A prospective study of 60 patients with abnormal uterine bleed in the peri and post menopausal age was conducted, for a period of three years. Histological specimens were studied for HPE and IHC for the markers PTEN and P53. Results: The mean age for hyperplastic and carcinomatous lesions was 44.9 years and 53.2 years respectively. 35% (21 cases) were endometrial hyperplasia and 65% (39 cases) of cases were endometrial carcinoma. Among endometrial carcinoma 87% are of endometrioid type and 13% are of other types, which include serous, clear and malignant mixed Mullerian type of carcinoma. IHC study showed that PTEN expression is higher in endometrial hyperplasia than endometrial carcinoma cases. Elevated P53 expression correlated with poor differentiation of endometrial cancer. P53 was found to be more in cases with FIGO staging III &IV compared to stage I & II (100% vs 18.1% p value= 0.0016) and grade 3 compared to grade 1&2 (50% vs 0 p value= 0.0116). Conclusion: Immuno histochemical biomarkers like PTEN and P53 may contribute to better tumor characterization and thus more precisely determine its clinical behavior. Key words: endometrial hyperplasia, endometrial carcinoma, PTEN, P53.