Glypican 3 expression in human nonneoplastic, preneoplastic, and neoplastic tissues: a tissue microarray analysis of 4,387 tissue samples.

Several studies have shown that glypican 3 (GPC3) could be a useful diagnostic marker for hepatocellular carcinoma (HCC) and for differentiating HCC from nonneoplastic and preneoplastic liver disease. To systematically investigate the epidemiology of GPC3 expression in the liver and in other organs and tissues, we used tissue microarray technology comprising 4,387 tissue samples from 139 tumor categories and 36 nonneoplastic and preneoplastic tissue types. The immunohistochemical expression of GPC3 was assessed semiquantitatively using a 10% cutoff score and was detected in 9.2% of nonneoplastic liver samples (11/119), 16% of preneoplastic nodular liver lesions (6/38), and 63.6% of HCCs (140/220), underlining the role of GPC3 in hepatocarcinogenesis. Furthermore, several other tumors revealed consistent expression of GPC3, including squamous cell carcinoma of the lung (27/50 [54%]), testicular nonseminomatous germ cell tumors (32/62 [52%]), and liposarcoma (15/29 [52%]).

[1]  H. Makhlouf,et al.  Glypican-3 expression in benign liver tissue with active hepatitis C: implications for the diagnosis of hepatocellular carcinoma. , 2008, Human pathology.

[2]  Robert A. Goulart,et al.  Glypican‐3 immunocytochemistry in liver fine‐needle aspirates , 2007, Cancer.

[3]  J. Jass,et al.  Loss of APAF-1 expression is associated with tumour progression and adverse prognosis in colorectal cancer. , 2007, European journal of cancer.

[4]  L. Terracciano,et al.  Diagnostic value of HSP70, glypican 3, and glutamine synthetase in hepatocellular nodules in cirrhosis , 2007, Hepatology.

[5]  J. Jass,et al.  A simple and reproducible scoring system for EGFR in colorectal cancer: application to prognosis and prediction of response to preoperative brachytherapy , 2007, British Journal of Cancer.

[6]  Ximing J. Yang,et al.  Glypican 3: A Novel Marker in Testicular Germ Cell Tumors , 2006, The American journal of surgical pathology.

[7]  Hiroyuki Aburatani,et al.  The glypican 3 oncofetal protein is a promising diagnostic marker for hepatocellular carcinoma , 2005, Modern Pathology.

[8]  K. Wakamatsu,et al.  Highly Sensitive Detection of Melanoma at an Early Stage Based on the Increased Serum Secreted Protein Acidic and Rich in Cysteine and Glypican-3 Levels , 2005, Clinical Cancer Research.

[9]  Hong-Yang Wang,et al.  Upregulation of Glypican‐3 expression in hepatocellular carcinoma but downregulation in cholangiocarcinoma indicates its differential diagnosis value in primary liver cancers , 2005, Liver international : official journal of the International Association for the Study of the Liver.

[10]  C. Lobe,et al.  Glypican-3 promotes the growth of hepatocellular carcinoma by stimulating canonical Wnt signaling. , 2005, Cancer research.

[11]  D. Luo,et al.  Expression and significance of tumor-related genes in HCC. , 2005, World journal of gastroenterology.

[12]  G. Sauter,et al.  Hepatocyte paraffin 1 expression in human normal and neoplastic tissues: tissue microarray analysis on 3,940 tissue samples. , 2004, American journal of clinical pathology.

[13]  K. Wakamatsu,et al.  Identification of Glypican-3 as a Novel Tumor Marker for Melanoma , 2004, Clinical Cancer Research.

[14]  M. Peters,et al.  Inhibition of Invasion and Metastasis by Glypican-3 in a Syngeneic Breast Cancer Model , 2003, Breast Cancer Research and Treatment.

[15]  Wen Shi,et al.  Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma. , 2003, Gastroenterology.

[16]  M. Kim,et al.  Glypican‐3 is overexpressed in human hepatocellular carcinoma , 2003, Cancer science.

[17]  H. Moch,et al.  Tissue microarrays for rapid linking of molecular changes to clinical endpoints. , 2001, The American journal of pathology.

[18]  J. Filmus,et al.  Glypican-3 expression is silenced in human breast cancer , 2001, Oncogene.

[19]  S. Selleck,et al.  Glypicans: proteoglycans with a surprise. , 2001, The Journal of clinical investigation.

[20]  Holger Moch,et al.  Microarrays of bladder cancer tissue are highly representative of proliferation index and histological grade , 2001, The Journal of pathology.

[21]  H. Friess,et al.  Enhanced glypican-3 expression differentiates the majority of hepatocellular carcinomas from benign hepatic disorders , 2001, Gut.

[22]  M. DeBaun,et al.  Simpson Golabi Behmel syndrome: progress toward understanding the molecular basis for overgrowth, malformation, and cancer predisposition. , 2001, Molecular genetics and metabolism.

[23]  N. Haboubi.  Pathology and genetics: Tumours of the digestive system , 2000 .

[24]  D. Sinnett,et al.  Expression of glypican 3 (GPC3) in embryonal tumors , 2000, International journal of cancer.

[25]  S. Jhanwar,et al.  Expression of GPC3, an X-linked recessive overgrowth gene, is silenced in malignant mesothelioma , 2000, Oncogene.

[26]  E Mahlamäki,et al.  Hormone therapy failure in human prostate cancer: analysis by complementary DNA and tissue microarrays. , 1999, Journal of the National Cancer Institute.

[27]  P. Marynen,et al.  Glypican-6, a New Member of the Glypican Family of Cell Surface Heparan Sulfate Proteoglycans* , 1999, The Journal of Biological Chemistry.

[28]  H. Moch,et al.  Tissue microarrays for gene amplification surveys in many different tumor types. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[29]  H. Moch,et al.  High-throughput tissue microarray analysis to evaluate genes uncovered by cDNA microarray screening in renal cell carcinoma. , 1999, The American journal of pathology.

[30]  D. Schlessinger,et al.  Frequent silencing of the GPC3 gene in ovarian cancer cell lines. , 1999, Cancer research.

[31]  J. Testa,et al.  OCI-5/GPC3, a Glypican Encoded by a Gene That Is Mutated in the Simpson-Golabi-Behmel Overgrowth Syndrome, Induces Apoptosis in a Cell Line–specific Manner , 1998, The Journal of cell biology.

[32]  Wei Cheng,et al.  Cloning and expression of a developmentally regulated transcript MXR7 in hepatocellular carcinoma: biological significance and temporospatial distribution. , 1997, Cancer research.

[33]  D. Schlessinger,et al.  Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome , 1996, Nature Genetics.

[34]  H. Edmondson,et al.  Primary carcinoma of the liver. A study of 100 cases among 48,900 necropsies , 1954, Cancer.

[35]  Cdm Fletcher,et al.  World Health Organization Classification of Tumours , 2002 .

[36]  L. Aaltonen,et al.  Pathology and genetics of tumours of the digestive system , 2000 .

[37]  M. Dietel,et al.  Expression of the novel mitoxantrone resistance associated gene MXR7 in colorectal malignancies. , 1998, International journal of clinical pharmacology and therapeutics.

[38]  A. Lander,et al.  The glypican family of heparan sulfate proteoglycans: major cell-surface proteoglycans of the developing nervous system. , 1996, Perspectives on developmental neurobiology.

[39]  D. Woodfield.  Hepatocellular carcinoma. , 1986, The New Zealand medical journal.