Balance of glandular and stromal Bcl2/Bax expression in pre-neoplastic and neoplastic endometrial tissues

Apoptosis is regulated by estrogen in normal endometrium and it is essential for the monthly sequential endometrial changes. In this study, epithelial and stromal expression of apoptosis regulated molecules; Bcl-2 and Bax in pathological endometrial lesions, their correlation with progression of endometrial carcinoma, and their association with estrogen receptor (ER) and progesterone receptor (PR) expression were investigated. Tissue sections of 39 endometrial carcinomas and 37 endometrial hyperplastic lesions were evaluated for Bcl-2, Bax, ER, and PR expression by immunohistochemistry. Bcl-2 and Bax expression was detected in most hyperplastic and in 77% and 82% of neoplastic endometrial lesions, respectively. The expression of both molecules was predominantly glandular; however concomitant stromal expression was also demonstrated. Glandular and stromal Bcl-2 and Bax expression was significantly reduced in endometrial carcinoma. There was a strong association between Bcl-2 and Bax expression in hyperplastic endometrium, in neoplastic lesions and in different histological subtypes, different grades and different FIGO stages of endometrial carcinoma at glandular, but not at the stromal level. The glandular expression of both molecules was significantly associated with ER and PR expression in hyperplastic lesions with loss of Bax/ER and Bax/PR association in neoplastic lesions. There was a strong association of stromal Bcl-2 with stromal ER expression in malignant endometrium and a strong association of stromal Bax with stromal ER in hyperplastic, but not in neoplastic endometrial lesions. In conclusion, disruption of hormonal control of Bax in endometrial tissue and subsequent disturbed stromal but not epithelial Bcl-2/Bax association could help early progression of endometrial carcinoma.

Endometrial carcinoma; Bcl-2, Bax; Glandular and stromal expression; Hormonal control.

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