TY - JOUR
T1 - Epidermal growth factor receptor expression correlates with poor survival in gastric adenocarcinoma from Mexican patients
T2 - A multivariate analysis using a standardized immunohistochemical detection system
AU - Gamboa-Dominguez, Armando
AU - Dominguez-Fonseca, Claudia
AU - Quintanilla-Martinez, Leticia
AU - Reyes-Gutierrez, Edgardo
AU - Green, Dan
AU - Angeles-Angeles, Arturo
AU - Busch, Raymonde
AU - Hermannstädter, Christine
AU - Nährig, Jörg
AU - Becker, Karl Friedrich
AU - Becker, Ingrid
AU - Höfler, Heinz
AU - Fend, Falko
AU - Luber, Birgit
N1 - Funding Information:
Dr Armando Gamboa-Dominguez obtained an award of the International Union Against Cancer (UICC ICRETT 552). This work has been partially supported by a UICC International Cancer Technology Transfer Fellowship and by a grant to Drs B. Luber, KF. Becker and H. Höfler from the Deutsche Forschungsgemeinschaft (SFB 456). The authors thank E. Samson, J. Mu. ller, S. Roth and N. Kink for excellent technical assistance. Neither author has a financial or other relation with Dako Corporation. Neither author received financial support from Dako Corporation or has a conflict of interest. The epidermal growth factor detection system was purchased from Dako Corporation, who did not influence the results of this study.
PY - 2004/5
Y1 - 2004/5
N2 - 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.
AB - 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.
KW - Anti-EGFR therapy
KW - EGFR reactivity score
KW - Epidermal growth factor receptor (EGFR)
UR - http://www.scopus.com/inward/record.url?scp=3042767348&partnerID=8YFLogxK
U2 - 10.1038/modpathol.3800085
DO - 10.1038/modpathol.3800085
M3 - Article
C2 - 15073595
AN - SCOPUS:3042767348
SN - 0893-3952
VL - 17
SP - 579
EP - 587
JO - Modern Pathology
JF - Modern Pathology
IS - 5
ER -