Original ArticlesGlypican 3: A Novel Marker in Testicular Germ Cell TumorsZynger, Debra L. MD*; Dimov, Nikolay D. MD*; Luan, Chunyan MS*; Tean Teh, Bin MD, PhD†; Yang, Ximing J. MD, PhD*Author Information *Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL †Laboratory of Cancer Genetics, Van Andel Research Institute, 333 Bostwick NE, Grand Rapids, MI Supported by the Lance Armstrong Foundation. Reprints: Ximing J. Yang, MD, PhD, Department of Pathology, Feinberg 7-334, Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern University, 251 East Huron Street, Chicago, IL 60611 (e-mail: firstname.lastname@example.org). Debra L. Zynger and Nikolay D. Dimov contributed equally to this work. Presented in abstract form at the United States and Canadian Academy of Pathology 2006 Annual Meeting in Atlanta. The American Journal of Surgical Pathology: December 2006 - Volume 30 - Issue 12 - p 1570-1575 doi: 10.1097/01.pas.0000213322.89670.48 Buy Metrics Abstract Glypican 3 (GPC3), a membrane-bound heparin sulfate proteoglycan, may play a role in promoting embryonic cell growth and differentiation. GPC3 is mutated in Simpson-Golabi-Behmel syndrome, characterized by tissue overgrowth and an increased risk of embryonal malignancies. Recently, GPC3 was reported to be one of the over-expressed genes in testicular yolk sac tumors by gene expression microarray analysis. However, the presence of the GPC3 protein in germ cell tumors has never been investigated. The purpose of the study was to investigate the GPC3 expression in various histologic components of testicular germ cell tumors using immunohistochemistry and to assess its possible utility as a diagnostic marker. Tumors from 71 patients were examined, including components of 42 seminomas, 37 embryonal carcinomas, 24 yolk sac tumors, 20 teratomas with mature elements, 16 teratomas with immature elements, and 7 choriocarcinomas. Cytoplasmic and membranous immunoreactivity was semiquantitatively evaluated. All yolk sac tumor (24/24) and choriocarcinoma (7/7) components were immunoreactive for GPC3, whereas only 38% of teratomas with immature elements and 8% of embryonal carcinomas expressed GPC3. There was no immunoreactivity in benign testicular tissue, intratubular germ cell neoplasia, seminomas (0/42), or teratomas with mature elements (0/20). We conclude that the oncofetal protein GPC3 is a novel immunohistochemical marker in testicular germ cell tumors with differential expression in defined histologic subtypes. Our findings suggest a possible role of GPC3 in tumor cell differentiation. Furthermore, GPC immunostaining may be useful in the pathologic diagnosis of nonseminomatous germ cell tumors, particularly yolk sac tumor, and choriocarcinoma. © 2006 Lippincott Williams & Wilkins, Inc.