Estrogen Receptor-β Expression in Human Testicular Germ Cell Tumors

• Published in: Clinical cancer research 2003-10, Vol.9 (12), p.4475-4482
• Main Authors: PAIS, Vernon, LEAV, Irwin, LAU, Kin-Mang, JIANG, Zhong, HO, Shuk-Mei
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Carcinoma, Embryonal - genetics; Carcinoma, Embryonal - metabolism; Carcinoma, Embryonal - pathology; Cell Differentiation; Endodermal Sinus Tumor - genetics; Endodermal Sinus Tumor - metabolism; Endodermal Sinus Tumor - pathology; Estrogen Receptor alpha; Estrogen Receptor beta; Germinoma - genetics; Germinoma - metabolism; Germinoma - pathology; Gynecology. Andrology. Obstetrics; Humans; Immunoenzyme Techniques; Male; Male genital diseases; Medical sciences; Middle Aged; Receptors, Androgen - genetics; Receptors, Androgen - metabolism; Receptors, Estrogen - genetics; Receptors, Estrogen - metabolism; Receptors, Progesterone - genetics; Receptors, Progesterone - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Neoplasm - genetics; Seminiferous Tubules - metabolism; Seminoma - genetics; Seminoma - metabolism; Seminoma - pathology; Teratoma - genetics; Teratoma - metabolism; Teratoma - pathology; Testicular Neoplasms - genetics; Testicular Neoplasms - metabolism; Testicular Neoplasms - pathology; Tumors
• ISSN: 1078-0432; 1557-3265

Purpose: Estrogen exposure has been linked to a risk for the development of testicular germ cell cancers. The effects of estrogen are now known to be mediated by estrogen receptor (ER)-α and -β receptor subtypes, but only ER-β has been found in human normal testis. The goal of the present study was to compare the localization and expression levels of these ER subtypes in testicular germ cell cancers (seminomas and nonseminomatous germ cell tumors) with normal testis. For completeness, expression of androgen and progesterone receptors was also investigated. Experimental Design: Immunohistochemistry was used to localize the expression of steroid receptors in 39 archival testicular germ cell cancers and 5 morphologically normal testes. Expression of the steroid receptors at the transcript level was semiquantified by reverse transcription-PCR in 5 paired fresh-frozen specimens of normal and neoplastic testes. Results: ER-α was not expressed in the human normal testis. It was also absent in all of the testicular germ cell cancers studied. In contrast, ER-β was strongly expressed in various germ cells of the normal testis. However, its expression was markedly diminished in seminomas, embryonal cell carcinomas, and in mixed germ cell tumors, at both transcriptional and translational levels. In contrast, ER-β remained highly expressed in endodermal sinus tumors and teratomas. Progesterone receptor, an estrogen-regulated gene, was localized to spermatagonia of the normal testis, but its expression dramatically reduced in seminomas. With the exception of spermatagonia, androgen receptor was found in all of the germ cells of the normal testis, but, aside from trace staining in 3 of 5 endodermal sinus tumor cells, it was not detected immunohistochemically in any other germ cell cancer. Conclusions: We confirm expression of ER-β, but not ER-α, in normal testicular cells, suggesting that only the former ER subtype mediates the action of estrogen in the human male gonad. Our results provide the first evidence that only ER-β is expressed in testicular germ cell tumors. Its expression is down-regulated in seminomas and embryonal cell carcinomas but remains high in endodermal sinus tumors and in teratomas. The observed differences in ER-β expression levels among different testicular germ cell tumors may reflect divergent pathways of differentiation/dedifferentiation of these neoplasms from a common precursor. Collectively, these findings provide a possible mechanistic link