Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Laboratory/Clinical Translational Research Oncology 144 DOI: 10.1159/000XXXXXX Immunohistochemical Study of Glypican 3 in Thyroid Cancer Kanako Yamanaka a Yasuhiro Ito b Noriko Okuyama a Katsuhisa Noda a Hitoshi Matsumoto a Hiroshi Yoshida b Akira Miyauchi b Mariana Capurro c Jorge Filmus c Eiji Miyoshi a a Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Osaka, and b Department of Surgery, Kuma Hospital, Kuma, Japan; c Divison of Molecular and Cell Biology, Sunnybrook and Women’s College Health Science Center, and Department of Medical Biophysics, University of Toronto, Toronto, Ont., Canada Introduction Glypican 3 (GPC3), a member of heparan sulfate pro- teoglycans, is attached to the cell surface by a glyco- sylphosphatidylinositol anchor [1, 2]. GPC3 was first identified as a gene which was developmentally expressed in rat intestines [3]. While a high expression of GPC3 was observed in fetal organs, it was scarcely detected in adult tissues [4]. Dysfunction of the GPC3 gene causes the Simpson-Golabi-Behmel syndrome, an X-linked disor- der characterized by pre- and postnatal overgrowth, and a broad spectrum of manifestations including macro- glossia, cleft palate, syndactyly, cystic and dysplastic kid- neys, congenital heart defects and umbilical/inguinal hernias [5]. In contrast, expression of GPC3 was increased in certain cancer tissues. Compared with other glypican family proteins, high and tumor-specific expression of GPC3 mRNA was observed in hepatocellular carcinoma (HCC) tissue [6]. This report was confirmed by recent DNA microarray analyses and immunohistochemical methods [7, 8]. Interestingly, serum levels of GPC3 mea- sured by an enzyme-linked immunosorbent assay were increased in patients with HCC (40–53%) [4, 9] . Since there was no correlation between GPC3 and -fetopro- tein values, 82% of HCC patients were positive for at least one of these two tumor markers. GPC3 was also identi- Key Words Glypican 3  Immunohistochemistry  Thyroid cancer Abstract In 123 patients with thyroid cancer, expression of glypican 3 (GPC3) was immunohistochemically investigated in tissue samples and the biological significance of GPC3 in thyroid cancer was examined. GPC3 was scarcely expressed in the normal thyroid gland, but was dramatically enhanced in cer- tain types of cancers: 100% in follicular carcinoma (20/20 cas- es) and 70% in papillary carcinoma (48/69 cases). Expression of GPC3 in follicular carcinoma was significantly higher than that of follicular adenoma (p ! 0.0019). In contrast, GPC 3 was not expressed in 17 cases of anaplastic carcinoma. A high expression of GPC3 mRNA was confirmed in cancer lesions, which were strongly positive for immunohistochemical staining. In 69 cases of papillary carcinoma, GPC3 was ex- pressed at an early stage, suggesting that GPC3 expression in thyroid cancer is an early event in developing papillary carcinoma. Further studies are required to determine bio- logical functions and molecular mechanisms underlying the upregulation of GPC3 in thyroid cancer. Copyright © 2008 S. Karger AG, Basel Received: October 10, 2007 Accepted after revision: November 15, 2007 Published online: $$$ Oncolog y Eiji Miyoshi Department of Molecular Biochemistry and Clinical Investigation Osaka University Graduate School of Medicine 1-7 Yamada-oka, Suita 565-0871 (Japan) Tel./Fax +81 6 6879 2590, E-Mail emiyoshi@sahs.med.osaka-u.ac.jp © 2008 S. Karger AG, Basel 0030–2414/08/0000–0000$24.50/0 Accessible online at: www.karger.com/ocl K.Y. and Y.I. contributed equally to this work. OCL144.indd 1 OCL144.indd 1 11.03.2008 11:06:13 11.03.2008 11:06:13