1. ¹Department of Pathology/Laboratory for Experimental Patho-Oncology, University Hospital of Rotterdam/Daniel, Josephine Nefkens Institute, Erasmus University Rotterdam, The Netherlands
2. ²Women's and Perinatal Pathology Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

Correspondence: Dr. L. H. J. Looijenga, Department of Pathology/Laboratory for Experimental Patho-Oncology, University Hospital Rotterdam/Daniel, Josephine Nefkens Institute, Erasmus University Rotterdam, Building Be, Room 430b, PO Box 1738, 3000 DR Rotterdam, The Netherlands. E-mail: looijenga@leph.azr.nl

Received 24 September 2001.

Abstract

VASA is so far the only known gene in mammals whose expression is specific for the germ cell lineage. We investigated the presence of VASA mRNA and protein in a series of germ cell tumors of different histologic subtypes and anatomic location, as well as in nongerm cell tumors such as testicular lymphomas and Leydig cell tumors. We detected VASA mRNA (by quantitative RT-PCR) and protein (by immunohistochemical staining) in normal spermatogenesis, seminoma (both classic and spermatocytic), carcinoma in situ (the precursor of classic seminoma and nonseminoma), dysgerminoma, and gonadoblastoma. VASA immunostaining was relatively weak in seminomas and dysgerminomas compared with spermatocytic seminomas, despite similar mRNA levels, suggesting that VASA is regulated in part by post-transcriptional mechanisms. A higher staining intensity compared with the invasive counterparts was observed in the precursor lesions (ie, carcinoma in situ and gonadoblastoma). No VASA mRNA or protein was detectable in nonseminomatous germ cell tumors (such as embryonal carcinoma, teratoma, and yolk sac tumor) and derived cell lines, or nongerm cell tumors such as lymphoma or Leydig cell tumor. These results provide direct evidence that some germ cell tumors retain germ cell characteristics, whereas other tumors of germ cell origin result from differentiation and loss of germ cell identity. Furthermore, these findings suggest that VASA is likely to serve as a useful and highly specific biomarker for germ cell tumors, particularly classic and spermatocytic seminoma/dysgerminoma, including their precursor stages.