Prognostic significance of inhibin/activin subunits (alpha, betaA and betaB) and steroid receptors (ER and PR) in human endometrial carcinoma

Introduction: Inhibins (INH) are dimeric glycoproteins, composed of an alpha-subunit (INH-a) and one of two possible beta-subunits (INH-bA or -bB), with substantial roles in human reproduction and in endocrine-responsive tumours. Aims of this study were to examine the expression of INH-a, -bA and -bB as well as steroid receptors (ER and PR) and evaluated their clinical significance in endometrial carcinomas.

Materials and Methods: 288 endometrial carcinoma cases were examined using immunohistochemistry with archival specimens. The findings were correlated with various clinicopathologic variables, including WHO grading, FIGO stage, histology, lymphnode involment, lymphangiosis.

Results: Immunoreactivity of INH-a, -bA and -bB and steroid receptors could be demonstrated in endometrial carcinomas. Patients whose tumours were negative for INH-a or PR were at much higher risk to develop recurrent and/or mortal disease as demonstrated by Kaplan-Meier analysis, while INH-b subunits and ER did not show any significance. In multivariate analysis, only the absence of INH-a turned out to be a independent risk factor in progression-free survival, cause-specific survival and overall survival (P <0.05), together with WHO grading, FIGO stage and lymphonodectomy.

Conclusions: This large study of 288 endometrial cancer cases demonstrate that loss or absence of INH-a as well as downregulation of PR expression determined by immunohistochemistry may be important tools to identify endometrial carcinoma cases at high risk of recurrence and/or death that are otherwise not detected by current clinical and pathologic evaluation. INH-a might have a tumour suppressor function in human endometrium as previously suggested for ovarian cancer in the mouse model. In addition, results of INH-a immunohistochemistry could contribute to planning postoperative follow-up and adjuvant therapy.