Abstract

Inhibins and activins are secreted polypeptides of the transforming growth factor-β superfamily that comprise a subfamily of dimeric, disulphide-linked proteins. Inhibins are composed of an alpha subunit and one of two possible beta subunits (βA or βB), while activins are homodimers of the beta subunits. Both inhibins and activins play substantial roles in human reproduction and endocrine-responsive tumors. However, the prognostic significance and clinical implications of inhibin-βA subunits in uterine endometrioid adenocarcinomas have not been defined. A series of 229 uterine endometrioid adenocarcinomas from a previously well-characterized cohort were re-evaluated for expression of the inhibin-βA subunit and correlated with several clinicopathological characteristics and clinical outcomes. Both staining intensity and analyses of a semi-quantitative score were used to evaluate inhibin-βA immunolabeling. The inhibin-βA subunit was present in malignant endometrioid uterine tissue, and was associated with myometrial invasion (p < 0.05). Univariate survival analysis demonstrated no differences in progression-free survival, cause-specific survival and overall survival for inhibin-βA using the median of the calculated semi-quantitative score. However, patients with a positive inhibin-βA, as identified by staining intensity, demonstrated significantly worse cause-specific survival (p < 0.05). Evaluation of staining intensity revealed better cause-specific survival in patients with negative or low inhibin-βA immunolabeling intensity. Therefore, although of some use, semi-quantification of immunohistochemical reactions might not be definitive for evaluation of the inhibin-βA subunit as a prognostic marker in endometrial cancer patients. Therefore, staining intensity evaluation should be performed in addition to semi-quantitative analysis. Further research is warranted to elucidate the possible implications of inhibin-βA and endometrial carcinogenesis.

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