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Immunohistochemical expression analysis of Cx43, Cx26, c-KIT and PlAP in contralateral testis biopsies of patients with non-seminomatous testicular germ cell tumor

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Abstract

Non seminomatous testicular germ cell tumors (NSTGCTs) express fetal stem cell markers and display dysregulation of connexin 43 expression. Persistence of fetal spermatogonial characteristics was implicated in the emergence of testicular germ cell tumors. The objective of this study was to analyze the tubular architecture in contralateral testes of patients with NSTGCT. We studied morphologic alterations, expression patterns of markers for the integrity of the germinal epithelium (gap junction proteins connexin 43 and 26), as well as of the embryonic markers c-KIT and placental alkaline phosphatase (PlAP), both established markers to detect carcinoma in situ (CIS). In all samples, tubules showing maturation of germ cells up to spermatozoa were observed. In addition, tubules with alterations in tubular architecture and with impaired spermatogenesis occurred. In tubules showing aberrant spermatogenesis, connexin 43 (Cx43) signal was down-regulated and a shift of signal from gap junctions to the cytoplasm occurred. Concomitantly, Cx26 was found highly up-regulated in tubules with incomplete and aberrant germ cell maturation. All testes exhibited single spermatogonia with positive reaction for c-KIT and a significant positive correlation was found between the mean number of c-KIT positive spermatogonia per tubule and the percentage of tubules presenting severely impaired spermatogenesis. Our data show alterations of the normal architecture of the germinal epithelium and disturbances of spermatogenesis in the contralateral testes of patients with NSTGCT in all cases evaluated. The concomitant occurrence of c-KIT positive spermatogonia and defects in tubular architecture is in line with the hypothesis that patients with NSTGCT suffer from disturbed germ cell development.

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Acknowledgments

The expert technical assistance of Ines Rammel is greatly acknowledged. We would like to thank Dr. Christa Freibauer, Institute of Clinical Pathology, Mistelbach General Hospital, for providing archival material and Michaela Leisser for assistance with PlAP and c-KIT staining. We are grateful to Mag. Christian Huber, Bernhard Gottlieb University for Dental Medicine, for his assistance with statistics.

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Authors and Affiliations

  1. Department for Cell- and Developmental Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, 1090, Vienna, Austria

    Marianne Steiner, Klara Weipoltshammer, Gerhard Viehberger & Christian Schöfer

  2. Department of Clinical Pathology, Mistelbach General Hospital, 2130, Mistelbach, Austria

    Eva-Maria Meixner

  3. Karl Landsteiner Institute for Andrology and Prostate Research, 2130, Mistelbach, Austria

    Gerhard Lunglmayr

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  1. Marianne Steiner
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  2. Klara Weipoltshammer
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  3. Gerhard Viehberger
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  4. Eva-Maria Meixner
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  5. Gerhard Lunglmayr
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  6. Christian Schöfer
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Correspondence to Christian Schöfer.

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Steiner, M., Weipoltshammer, K., Viehberger, G. et al. Immunohistochemical expression analysis of Cx43, Cx26, c-KIT and PlAP in contralateral testis biopsies of patients with non-seminomatous testicular germ cell tumor. Histochem Cell Biol 135, 73–81 (2011). https://doi.org/10.1007/s00418-010-0769-8

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  • DOI: https://doi.org/10.1007/s00418-010-0769-8

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