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[Cancer Research 63, 2244-2250, May 1, 2003]
© 2003 American Association for Cancer Research

Tumor Biology

POU5F1 (OCT3/4) Identifies Cells with Pluripotent Potential in Human Germ Cell Tumors1

Leendert H. J. Looijenga2,,3, Hans Stoop3, Hubert P. J. C. de Leeuw, Carlos A. de Gouveia Brazao, Ad J. M. Gillis, Kees E. P. van Roozendaal, Everardus J. J. van Zoelen, Rob F. A. Weber, Katja P. Wolffenbuttel, Herman van Dekken, Friedemann Honecker, Carsten Bokemeyer, Elizabeth J. Perlman, Dominik T. Schneider, Juha Kononen, Guido Sauter and J. Wolter Oosterhuis

Pathology/Lab. for Exp. Patho-Oncology [L. H. J. L., H. S., H. P. J. C. d. L., A. J. M. G., J. W. O.], Pathology [H. v. D.], Josephine Nefkens Institute; Andrology [C. A. d. G. B., R. F. A. W.], Pediatric Urology [K. P. W.], Erasmus MC, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands; Department of Cell Biology, University of Nijmegen, Toernooiveld 1, 6525 ED, Nijmegen, The Netherlands [K. E. P. v. R., E. J. J. v. Z.]; Department of Hematology/Oncology, University of Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen [F. H., C. B.]; Children’s Memorial Hospital, 2300 Children’s Plaza, Chicago, IL 60614-3394, USA [E. J. P.], Pediatric Hematology and Oncology, Heinrich Hein University, Moorenstrasse 5, 40225, Düsseldorf, Germany [D. T. S.]; Diomeda Life Sciences, Inc., 820 Hummingbird Court, Sun Praine, WI 53590, USA [J. K.]; and Department of Pathology, University of Basel, Schoenbeinstrasse 40, CH-4003 Basel, Switzerland [G. S.]

Human germ cell tumors (GCTs) may have variable histology and clinical behavior, depending on factors such as sex of the patient, age at clinical diagnosis, and anatomical site of the tumor. Some types of GCT, i.e., the seminomas/germinomas/dysgerminomas and embryonal carcinomas (the stem cell component of nonseminomas), have pluripotent potential, which is demonstrated by their capacity to differentiate into somatic and/or extraembryonic elements. Although embryonal carcinoma cells are intrinsically pluripotent, seminoma/germinoma/dysgerminoma cells, as well as their precursor carcinoma in situ/gonadoblastoma cells, have the phenotype of early germ cells that can be activated to pluripotency. The other types of GCT (teratomas and yolk sac tumors of infants and newborn, dermoid cyst of the ovary, and spermatocytic seminoma of elderly) are composed of (fully) differentiated tissues and lack the appearance of undifferentiated and pluripotent stem cells. OCT3/4, a transcription factor also known as OTF3 and POU5F1, is involved in regulation of pluripotency during normal development and is detectable in embryonic stem and germ cells. We analyzed the presence of POU5F1 in GCT and other tumor types using immunohistochemistry. The protein was consistently detected in carcinoma in situ/gonadoblastoma, seminomas/germinoma/dysgerminoma, and embryonal carcinoma but not in the various types of differentiated nonseminomas. Multitumor tissue microarray analysis covering >100 different tumor categories and 3600 individual cancers verified that POU5F1 expression is specific for particular subtypes of GCT of adults. No protein was observed in GCT of newborn and infants, spermatocytic seminomas, and the various tumors of nongerm cell origin. In addition, no difference in staining pattern was found in chemosensitive and chemoresistant GCT of adults. These results indicate preservation of the link between POU5F1 and pluripotency, as reported during normal development, after malignant transformation. Therefore, POU5F1 immunohistochemistry is an informative diagnostic tool for pluripotent GCT and offers new insights into the histological heterogeneity of this cancer.




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