title: Epidermal growth factor receptor expression correlates with poor survival in gastric adenocarcinoma from Mexican patients: a multivariate analysis using a standardized immunohistochemical detection system.
abstract: The aim of the study was to determine epidermal growth factor receptor (EGFR) expression in gastric adenocarcinoma by standardized immunohistochemistry and to correlate EGFR expression with clinical features and patient survival. EGFR expression was investigated in paraffin sections of resection specimens of 89 gastric carcinomas from Mexican Mestizo patients using standardized immunohistochemistry with antigen retrieval (Dako EGFRpharmDx assay detection system). Membrane staining of EGFR was evaluated in the neoplastic cells and graded using a semiquantitative score (0-3+). Of the 89 carcinomas examined, staining of neoplastic cells was weak in 17 (19.1%, score 1+), moderate in 16 (18.0%, score 2+), and strong in nine cases (10.1%, score 3+). EGFR reactivity was heterogeneous, frequently showing completely negative up to 3+ positive areas within an individual tumor. EGFR reactivity score correlated with distant metastases (P=0.002) and clinical stage (P=0.033). EGFR score 0/1+ was significantly associated with an increase in patient survival when compared to score 2+/3+ (P=0.0006). In a multivariate analysis, EGFR positive cells in muscularis or subserosa (P=0.004), distant metastases (P=0.016) and residual disease (P=0.039) were significantly correlated with decreased survival. The prognosis was associated with the EGFR reactivity score (P=0.003), distant metastases (P=0.0001) and residual disease (P=0.012) in a univariate analysis. EGFR reactivity in neoplastic cells is an independent prognostic factor in gastric adenocarcinoma. The relevance of the heterogeneity in EGFR expression with regard to tumor progression, metastasis and anti-EGFR therapy needs to be studied.
authors.affiliation: Department of Pathology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico.
authors.forename: Armando
authors.initials: A
authors.lastname: Gamboa-Dominguez
authors.forename: Claudia
authors.initials: C
authors.lastname: Dominguez-Fonseca
authors.forename: Leticia
authors.initials: L
authors.lastname: Quintanilla-Martinez
authors.forename: Edgardo
authors.initials: E
authors.lastname: Reyes-Gutierrez
authors.forename: Dan
authors.initials: D
authors.lastname: Green
authors.forename: Arturo
authors.initials: A
authors.lastname: Angeles-Angeles
authors.forename: Raymonde
authors.initials: R
authors.lastname: Busch
authors.forename: Christine
authors.initials: C
authors.lastname: Hermannstädter
authors.forename: Jörg
authors.initials: J
authors.lastname: Nährig
authors.forename: Karl-Friedrich
authors.initials: KF
authors.lastname: Becker
authors.forename: Ingrid
authors.initials: I
authors.lastname: Becker
authors.forename: Heinz
authors.initials: H
authors.lastname: Höfler
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
authors.forename: Birgit
authors.initials: B
authors.lastname: Luber
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008800:Mexico; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D016019:Survival Analysis
chemical_list: D066246:ErbB Receptors