Differential Expression Patterns of PTEN in Cyclic, Hyperplastic and Malignant Endometrium: Its Relation with ER, PR and Clinicopathological Parameters.

UNLABELLED: PTEN is a tumor suppressor gene, which is frequently mutated and involved in the control of cell proliferation, differentiation, and apoptosis in a variety of human tumors including endometrium. We hypothesized that PTEN expression in endometrium is variable throughout the menstrual cycle as well as different endometrial lesions, and that steroid hormones regulate PTEN expression because PTEN is critical in many steroid-sensitive tissues such as endometrium.

AIM OF WORK: In this study, we aimed to assess the relationships between PTEN expression and estrogen (ER), progesterone receptors (PR) in normal endometrium, hyperplasia and endometrial carcinoma. We also evaluated the relationship between PTEN expression and clinicpathologic parameters including tumor grade, stage and myomrtial invasion in endometrial carcinoma.

METHODS: Specimens included 12 cyclical endometrium, 12 cases endometrial hyperplasia without atypia, 8 cases atypical endometrial hyperplasia and 35 endometrial carcinoma specimens. Immunohistochemical staining for PTEN protein, ER and PR was performed with the Streptavidin-biotin method on formalin-fixed and paraffinembedded tissue samples. PTEN, ER and PR expression was represented as the staining score.

RESULTS: Immunohistochemistry showed that PTEN, ER and PR were positive for nuclei of cells. The PTEN staining score of normal endometrium was higher in the proliferative phase than in the secretory phase. The PTEN scores in atypical hyperplasia and endometrial carcinoma were significantly lowered than those for cyclic and hyperplasia without atypia. In endometrial carcinoma, PTEN expression was significantly correlated with histological grade while no significant associations with either stage or myometrial invasion were seen. Significant correlations were detected between PTEN and PR in EC cases and between PR and ER in all lesions, while no correlation was seen between ER and PTEN in different lesions.

CONCLUSIONS: PTEN expression has been changes throughout the menstrual cycle. We suggest that PTEN is involved in the early stages of endometrial carcinogenesis. In endometrial carcinomas, loss of PTEN expression is involved in tumor cell differentiation.

KEY WORDS: PTEN - Cyclic - Hyperplastic - Malignant endometrium - Estrogen receptor - Progesterone Receptor.