Protein Overexpression and Gene Amplification of Epidermal Growth Factor Receptor in Nonsmall Cell Lung Carcinomas: Comparison of Four Commercially Available Antibodies by Immunohistochemistry and Fluorescence In Situ Hybridization Study
HJ Lee, XH Xu, GY Choe, DH Chung, JW Seo, CT Lee, SH Jheon, SW Sung, JH Chung. Seoul National University College of Medicine, Seongnam-Si, Gyeonggi-do, Republic of Korea; Seoul National University Bundang Hospital, Seongnam-Si, Gyeonggi-do, Republic of Korea
Background: Epidermal Growth Factor Receptor (EGFR) overexpression in nonsmall cell lung carcinomas (NSCLC) is variable ranged from 17% to 71.6% and prognostic value for survival in patients remains controversial. We tried to investigate 1) EGFR protein expression using four different antibodies 2) the correlation between protin overexpression and EGFR gene amplification and 3) the correlation between EGFR genetic status and clinicopathologic features in NSCLC.
Design: We examined EGFR protein expression using four different antibodies including Dako EGFR pharmDx kit (Clone 2-18C9), Zymed EGFR kit (Clone 31G7), Novocastra (Clone EGFR 113) and Dako (Clone H11) by immunohistochemical analysis. The protein overexpression was compared to gene amplification status by fluorescence in situ hybridization (FISH).
Results: EGFR protein overexpression was observed in 51% of tumors with Dako EGFR pharmDx kit (Clone 2-18C9), in 56% with Zymed EGFR kit (Clone 31G7), in 18% with Novocastra (Clone EGFR 113) and in 5% with Dako (Clone H11), respectively (p <0.01). Both Zymed and Dako pharmDx kit were more sensitive than the Dako test using clone H11 and Novocastra Clone EGFR 113. EGFR overexpression is most prominent in squamous cell carcinomas (SCC) than adenocarcinomas (ADC) (71% vs. 48%, p =0.001 in Zymed; 61% vs. 45%, p =0.011 in Dako pharmDx kit, respectively). EGFR FISH-positivity was observed in 45% of the NSCLC patients. Protein expression levels significantly correlated with the gene copy number per tumor cell (p =0.000). EGFR overexpression with Zymed clone 31G7 had significant influence on shortened progression-free survival in ADC (p =0.037).
Conclusions: Our data showed a higher percentage of positive cells detected by Zymed and Dako pharmDx tests, whatever scoring system. EGFR protein overexpression rate varies from 5% to 71% according to different antibody clones and histologic types. EGFR protein expression detected by Zymed and Dako pharmDx was significantly associated with a high EGFR gene copy number. EGFR gene amplification predicted a poor prognosis in NSCLC, especially ADC. Protein overexpression bears only prognostic informative value in ADC.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 234, Tuesday Afternoon