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Gene Expression Profiling in Seminoma and Nonseminoma

From the Institute of Radiobiology of the Federal Armed Forces, Munich; Departments of Urology and Internal Medicine, Federal Armed Forces Hospital, Ulm; Department of Urology, Klinikum Kassel GmbH, Kassel; Department of Urology, Federal Armed Forces Hospital, Hamburg, Germany

Address reprint requests to Hans Ulrich Schmelz, MD, Institute of Radiobiology, Federal Armed Forces, Ernst-von-Bergmann-Kaserne, Neuherbergstr 11, 80937 Munich, Germany; e-mail: michaelabend{at}bundeswehr.org

PURPOSE: Gene expression profiles of seminoma were compared with nonseminoma to get insights into tumorigenesis.

MATERIALS AND METHODS: Eleven testicular tumor biopsies (five pure seminoma, six nonseminoma; pT1N0M0 to pT2N2M1) and biopsies from unaffected sites were analyzed once per patient using a macroarray (1,176 genes). On the same patients, six genes were validated using real-time quantitative (RTQ) polymerase chain reaction (PCR). Additionally, in a separate cohort of 19 patients, 24 genes selected from the macroarray were measured using RTQ-PCR.

RESULTS: (1) The agreement in gene expression was 94% between the two methods and two different patient cohorts. (2) Two features in gene expression were independent of the tumor entity: Most changes of gene expression occurred in five functional groups like "cell cycle" and "apoptosis." Genes within these groups were almost similarly (> 80%) up- or downregulated. (3) Nonseminoma were characterized by downregulated genes (75%), but in seminoma, upregulated genes (64%) prevailed. Furthermore, 64.4% of those genes that were differentially expressed in both tumor entities were usually upregulated in seminoma but downregulated in nonseminoma. A reverse pattern was found in 24.4% of such genes. Eleven percent of these genes showed a similar up- or downregulation in gene expression in both tumor entities.

CONCLUSION: Seminoma in this preliminary study can be differentiated from nonseminoma due to almost opposing gene expression profiles (89% of the significantly differentially expressed genes) and are in line with the histological discrimination of both tumor entities. Underlying mechanisms and implications regarding the origin and tumor progression of both entities are discussed.

Supported by the German Ministry of Defense.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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