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Letter to the Editor

Are all testicular seminomas of animals in fact spermatocytic seminomas? Towards a comprehensive investigation.

Animal models, either spontaneously occurring or induced have been proven to be highly informative for cancer research in general. We demonstrated in 1994 that the canine testicular seminomas are most likely not a proper model for testicular seminomas of adolescent and young (mainly) Caucasian males, but of spermatocytic seminomas of elderly men¹. Based on recent data, tools have become available to explore this hypothesis in more detail. These include investigation of diagnostic markers²; detection of the protein OCT3/4-POU5F1 is a proper diagnostic marker for seminomas³, while SSX and DMRT1 are specific for spermatocytic seminomas⁴. Besides marker expression, the chromosomal constitution of the tumor cells is also informative to distinguish seminomas from spermatocytic seminomas^4–6. Human seminomas show characteristically overrepresentation of the short of chromosome 12, while chromosome 9 is specifically gained in spermatocytic seminomas⁴.

Our working model is that all tumors classified as seminomas in animals are in fact spermatocytic seminomas. To test this hypothesis, we would like to develop a tissue archive, to be organized in a so-called tissue micro array⁷ of seminomatous tumors diagnosed in animals. These will be investigated for marker expression by immunohistochemistry and genomic studies using in situ hybridization techniques. This will shed light on the pathogenesis of human germ cell tumors, and elucidate the value of spontaneous animal tumors in this context.

We therefore ask the Veterinary Pathology Community to assist development of a unique tissue archive of seminomatous tumors of all species. For that purpose we would like to receive representative paraffin-embedded tissue.

Leendert H.J. Looijenga, J. Wolter Oosterhuis

Department of Pathology

Erasmus MC-University Medical Center Rotterdam

Daniel den Hoed Cancer Center

Josephine Nefkens Institute

Dr. Molewaterplein 50

3015 GE Rotterdam, The Netherlands

Tel./fax: (31) 10 4088329/65

e-mail: l.looijenga{at}erasmusmc.nl

References

1. Looijenga LHJ, Olie RA, Van der Gaag I, van Sluijs FJ, Matoska J, Ploem-Zaaijer J, Knepfle C, Oosterhuis JW. Seminomas of the canine testis; counterpart of spermatocytic seminoma of men?. Lab Invest 71:490–496, 1994[ISI][Medline]
2. Stoop H, Van Gurp RHJ, L.M, De Krijger R, Geurts van Kessel A, Koberle B, Oosterhuis JW, Looijenga LHJ. Reactivity of germ cell maturation stage-specific markers in spermatocytic seminoma: diagnostic and etiological implications. Lab Invest 81:919–928, 2001[ISI][Medline]
3. Looijenga LHJ, Stoop H, De Leeuw PJC, De Gouveia Brazao CA, Gillis AJM, Van Roozendaal KEP, Van Zoelen EJJ, Weber RFA, Wolffenbuttel KP, Van Dekken H, Honecker F, Bokemeyer C, Perlman EJ, Schneider DT, Kononen J, Sauter G, Oosterhuis JW. POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors. Cancer Res 63:2244–2250, 2003[Abstract/Free Full Text]
4. Looijenga LHJ, Hersmus R, Gillis A, Stoop J, Van Gurp RJLM, Veltman J, Beverloo B, Van Drunen E, Geurts van Kessel A, Reijo Pera R, Schneider DT, Summersgill B, Shipley J, McIntyre A, Van der Spek P, Schoenmakers E, Oosterhuis JW. Genomic and expression profiling of human spermatocytic seminomas; primary spermatocyte as tumorigenic precursor and DMRT1 as candidate chromosome 9-gene. Cancer Res 2006, in press
5. Rosenberg C, Mostert MC, Schut TB, van de Pol M, van Echten J, de Jong B, Raap AK, Tanke H, Oosterhuis JW, Looijenga LH. Chromosomal constitution of human spermatocytic seminomas: comparative genomic hybridization supported by conventional and interphase cytogenetics. Genes Chromosom & Cancer 23:286–291, 1998[CrossRef][ISI][Medline]
6. Maiolino P, Restucci B, Papparella S, Paciello O, De Vico G. Correlation of nuclear morphometric features with animal and human World Health Organization International Histological Classifications of canine spontaneous seminomas. Vet Pathol 41:608–611, 2004[Abstract/Free Full Text]
7. Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4:844–847, 1998[CrossRef][ISI][Medline]

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