• Katharina Biermann, Lukas Carl Heukamp, Klaus Steger, Hui Zhou, Folker Ernst Franke, Ines Guetgemann, Violetta Sonnack, Ralph Brehm, Johannes Berg, Patrick Jan Bastian, Stefan Cajetan Müller, Lihua Wang-Eckert, Hubert Schorle, and Reinhard Büttner.
• Institute of Pathology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany. katharina.biermann@ukb.uni-bonn.de
• Anticancer Res. 2007 Sep 1; 27 (5A): 3091-100.

BackgroundThere is only limited knowledge about gene expression in human testicular germ cell tumors of adolescents and adults (TGCTs), and, in particular in its preinvasive stage intratubular germ cell neoplasia unclassified (IGCNU).Materials And MethodsGlobal gene expression was studied in 10 invasive human testicular germ cell tumors (TGCTs), 7 intratubular germ cell neoplasia unclassified (IGCNU) and 3 normal testes. The pattern of expression of several genes was studied by immunohistochemistry on tissue microarrays containing 126 TGCTs, IGCNU, normal testes and in 5 fetal testes.ResultsRAS-related genes (KRAS2, RALA, RAB39B) and various core markers of embryonic stem cells were overexpressed in IGCNU compared to normal testes. CD9, PODXL and centromere-specific histone-H3-like protein CENPA were specifically identified in IGCNU, seminomas, embryonal carcinomas and in fetal gonocytes. Embryonic stem cell regulator SOX2 and downstream targets of the Nodal pathway were up-regulated in embryonal carcinoma only but not in IGCNU/seminoma. Preliminary data revealed that the expression profile of IGCNU is dependent on the histology of the adjacent invasive tumor.ConclusionOur study determined the genes involved in early pathogenetic events of neoplastic germ cell formation, provided new insights into genetic pathways driving the transition of embryonal carcinoma and seminoma from IGCNU and identified new biomarkers of neoplastic germ cells such as CD9, CENPA and PODXL.

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