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HER2 in gastric cancer: a digital image analysis in pre-neoplastic, primary and metastatic lesions.
MedLine Citation:
PMID:  23348899     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The assessment of human epidermal growth factor receptor 2 (HER2) status in gastric cancer is crucial in selecting patients who may benefit from targeted therapy, yet heterogeneous expression could represent an important drawback for HER2 testing. We aimed to analyze (i) HER2 heterogeneity in primary gastric cancers, pre-neoplastic and metastatic lesions and (ii) HER2 prognostic role. We studied 292 surgically resected primary gastric carcinomas and constructed 21 tissue microarrays including tumor tissue cores, invasive front, paired lymph node metastasis, low- and high-grade dysplasia. Microarrays were immunohistochemically stained with HER2 antibody and digitally scanned. Novel digital analysis algorithms were developed to score HER2 expression. Fluorescence in situ hybridization was performed on equivocal cases. HER2-positive cases were 13% and heterogeneous HER2 expression was observed in 71% of positive samples. Analysis of HER2 status in tumor and tumor invasive front demonstrate concordance in 177 cases (88%). Comparison of HER2 expression in primary cancer and synchronous lymph node metastasis exhibited discordant status in 14% of cases. Dysplastic epithelium surrounding the tumor showed immunohistochemical score 2 or 3 in 19% of high-grade and in 9% of low-grade dysplastic samples. HER2 status was significantly associated with intestinal-type carcinomas (P=0.018) and prognosis since patients with primary HER2-positive tumor showed decreased overall survival (P=0.006). Intratumoral HER2 expression heterogeneity and variable lymph node metastases status strongly suggest evaluating more than one sample and, if available, metastatic foci for routinely HER2 testing.Modern Pathology advance online publication, 25 January 2013; doi:10.1038/modpathol.2012.228.
Authors:
Nicola Fusco; Elena Guerini Rocco; Claudia Del Conte; Caterina Pellegrini; Gaetano Bulfamante; Franca Di Nuovo; Solange Romagnoli; Silvano Bosari
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-25
Journal Detail:
Title:  Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc     Volume:  -     ISSN:  1530-0285     ISO Abbreviation:  Mod. Pathol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8806605     Medline TA:  Mod Pathol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Division of Pathology, Department of Pathophysiology and Transplantation, University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
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