title: Coexpression of EGFR and HER-2 in pancreatic ductal adenocarcinoma: a comparative study using immunohistochemistry correlated with gene amplification by fluorescencent in situ hybridization.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is the major pancreatic tumor and carries an extremely poor prognosis. Coexpression of epidermal growth factor receptor (EGFR) and the HER-2 oncoprotein has been reported to be related to the invasion and an adverse clinical outcome of human pancreatic ductal adenocarcinomas. HER-2 amplification, as determined by fluorescent in situ hybridization (FISH) analysis, has been identified as a positive predictor of response to EGFR tyrosine kinase inhibitor treatment in some other cancers. The aim of this study was to investigate the coexpression rate and amplification status of HER-2 oncogene in EGFR positive pancreatic ductal adenocarcinoma (PDAC) by immunohistochemistry and FISH. Overexpression of EGFR (>or=2+) was seen in 65% (21/32) of the study cases. EGFR gene amplification was not detected in any of the 32 PDACs. Overexpression of HER-2 protein (>or=2+) was seen in 17% (5/28) of the study cases and in 24% (5/21) of EGFR positive cases. None of the EGFR negative tumors showed HER-2 overexpression or gene amplification. The HER-2 gene locus was amplified in 11% (3/28) of the study cases and in 14% (3/21) of EGFR positive PDACs. There was 60% concurrence between HER-2 gene amplification and HER-2 protein expression in this study. These results suggest that HER-2 is an important cooperating member of the EGFR signal pathway in a subset of PDAC.
authors.affiliation: Department of Pathology, M227, The Methodist Hospital, Houston, TX 77030, USA. yzdancer@tmh.tmc.edu
authors.forename: Jane
authors.initials: J
authors.lastname: Dancer
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Takei
authors.forename: Jae Y
authors.initials: JY
authors.lastname: Ro
authors.forename: Mary
authors.initials: M
authors.lastname: Lowery-Nordberg
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases