Inhibin-βA subunit immunolabeling as a prognostic factor in endometrioid adenocarcinomas: a matter of evaluation?
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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.
KeywordsEndometrial cancer Endometrioid adenocarcinoma Immunohistochemistry Inhibin-βA Prognosis Survival
The authors would like to thank Dr. S. Worbs, Dr. N. Shabani, Mrs. C. Kuhn, Mrs. S. Kunze, Mrs. S. Schulze, Dr. D. Dian, Dr. A. Gingelmaier, Dr. C. Schindlbeck, Dr. A. Brüning, Dr. U. Jeschke, Prof. H. Sommer and Prof. K. Friese for their help in conducting the primary study. Additionally, he would like to thank Prof. D. Hölzel; Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University Munich and Mr. M. Schmidt of the Munich Tumor Registry for supplying the survival data. This study was partially supported by the FöFoLe program of the Ludwig-Maximilians-University Munich (297/03), the Friedrich-Baur-Institute Munich and the Weigland Stipendium Program of the Ludwig-Maximilians-University Munich for I. Mylonas. I. Mylonas is founded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG BR 3641/3-1).
Conflict of interest
The author declares that he has no competing interests and no conflicts of interest. He received a lecture fee in the year 2006 with the title “Endometrial cancer and inhibin subunits”. The author does not have any financial, personal, political, intellectual or religious interests in publishing this article.
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