Inhibin-alpha subunit expression in uterine endometrioid adenocarcinomas and endometrial cancer cell lines: a potential prognostic factor.

摘要

Inhibins/activins are secreted polypeptides of the transforming growth factor-beta superfamily, forming a family of dimeric, disulphide-linked proteins. Inhibins are composed of an alpha-subunit and one of two possible beta-subunits. Both inhibins and activins have substantial roles in human reproduction and in endocrine-responsive tumors. However, the prognostic significance and clinical implications of the inhibin-alpha subunits in uterine endometrioid adenocarcinomas is still not clearly defined. A series of 231 uterine endometrioid adenocarcinomas of a previous well-characterized cohort were re-evaluated for the expression of the inhibin-alpha subunit and correlated with several clinicopathological characteristics and clinical outcome. Additionally, several endometrial epithelial cell lines (Ishikawa plus and minus, HEC-1A, HEC-1B and RL95-2) were analyzed for the expression of this subunit using immunohistochemical and molecular biological techniques. A significant association between the inhibin-alpha subunit and histological grade, surgical staging and myometrial invasion was demonstrated. Survival analysis demonstrated that inhibin-alpha immunoreactivity significantly affected progression-free, cause-specific and overall survival of patients with endometrioid adenocarcinomas. The analyzed endometrial cancer cell lines can also synthesize this subunit. Inhibin-alpha seems to have a substantial role in the carcinogenesis and pathology of uterine endometrioid carcinomas, and might be used as a marker to identify high-risk patients and may aid in the selection of patients for a more aggressive adjuvant therapy. Since uterine cancer cell lines express the inhibin-alpha subunit, they constitute adequate in vitro models for assessing its function in endometrial carcinogenesis. However, further research is warranted to elucidate the possible implications of inhibin-alpha in endometrial carcinogenesis.