Original Article

Modern Pathology (2004) 17, 579–587, advance online publication, 9 April 2004; doi:10.1038/modpathol.3800085

Epidermal growth factor receptor expression correlates with poor survival in gastric adenocarcinoma from Mexican patients: a multivariate analysis using a standardized immunohistochemical detection system

Armando Gamboa-Dominguez1, Claudia Dominguez-Fonseca1, Leticia Quintanilla-Martinez2, Edgardo Reyes-Gutierrez1, Dan Green3, Arturo Angeles-Angeles1, Raymonde Busch4, Christine Hermannstädter5, Jörg Nährig5, Karl-Friedrich Becker2,5, Ingrid Becker5, Heinz Höfler2,5, Falko Fend5 and Birgit Luber5

  1. 1Department of Pathology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
  2. 2GSF-Forschungszentrum für Umwelt und Gesundheit, Institut für Pathologie, Neuherberg, Germany
  3. 3Department of Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
  4. 4Technische Universität München, Klinikum rechts der Isar, Institut für Medizinische Statistik und Epidemiologie, München, Germany
  5. 5Technische Universität München, Klinikum rechts der Isar, Institut für Allgemeine Pathologie und Pathologische Anatomie, München, Germany

Correspondence: Dr Birgit Luber, Trogerstr. 18, 81675 München, Germany. E-mail: luber@lrz.tum.de

Received 20 June 2003; Revised 13 November 2003; Accepted 16 November 2003; Published online 9 April 2004.

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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 EGFRpharmDxTM 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.

Keywords:

epidermal growth factor receptor (EGFR), EGFR reactivity score, anti-EGFR therapy

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