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Ann Thorac Surg 2008;85:216-223. doi:10.1016/j.athoracsur.2007.07.046
© 2008 The Society of Thoracic Surgeons
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Inderpal S. Sarkaria
Michael I. Ebright
Valerie W. Rusch
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Original Articles: General Thoracic

Epidermal Growth Factor Receptor Signaling in Adenocarcinomas With Bronchioloalveolar Components

Inderpal S. Sarkaria, MDa,c,*, Maureen F. Zakowski, MDb,d, Duykhanh Pham, MDa,c, Michael Hezel, BAa, Michael I. Ebright, MDc, Shaokun Chuai, MAe, Ennapadam S. Venkatraman, PhDe, Mark G. Kris, MDb,f, Valerie W. Rusch, MDb,c, Bhuvanesh Singh, MDa,c

a Laboratory of Epithelial Cancer Biology, Memorial Sloan-Kettering Cancer Center, New York, New York
b Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York
c Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
d Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York
e Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York
f Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York

Accepted for publication July 11, 2007.

* Address correspondence to Dr Sarkaria c/o Dr Singh, Memorial Sloan-Kettering Cancer Center, Division of Head & Neck Surgery, 1275 York Ave, New York, NY 10021 (Email: singhb{at}mskcc.org).

Background: Epidermal growth factor receptor (EGFR) has gained importance in non–small cell lung cancer given impressive responses to agents targeting this molecule, particularly in bronchioloalveolar carcinoma (BAC) and adenocarcinomas, mixed subtype, with BAC components (adeno/BAC). This study assesses EGFR signaling in these tumors.

Methods: One hundred fifty tumors were classified as BAC or adeno/BAC. Tumor marker expression was determined by immunohistochemistry. Correlations with expression were examined for all tumors (BAC and adeno/BAC), and by BAC and adeno/BAC subset analyses.

Results: Positive immunophenotype was observed in 40.6% of tumors for EGFR, 51.3% for p-AKT, 58.7% for p-ERK, and 28.0% for PTEN, with increased overexpression of EGFR (p = 0.025) and p-AKT (p < 0.0001) in adeno/BAC. Epidermal growth factor receptor immunophenotype was greater in never-smokers (p = 0.008) and correlated with improved overall survival (p = 0.018). On subset analysis, EGFR correlated with improved overall survival (p = 0.05) and disease-free interval (p = 0.044) only in adeno/BAC. Epidermal growth factor receptor independently predicted improved disease-free interval in adeno/BAC (p = 0.03; hazard ratio, 0.47; 95% confidence interval, 0.23 to 0.94).

Conclusions: Overexpression of EGFR in lung adenocarcinomas with components of BAC histology correlate with never-smoker status and improved overall survival and disease-free interval. Epidermal growth factor receptor immunophenotype may be a useful predictor of clinical outcomes in this tumor subset.






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