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Laboratory and Animal Investigations |

Small Tumor Size and Limited Smoking History Predicts Activated Epidermal Growth Factor Receptor in Early-Stage Non-small Cell Lung Cancer*

Zhong Zheng, PhD; Gerold Bepler, MD, PhD; Alan Cantor, PhD; Eric B. Haura, MD
Author and Funding Information

*From the Thoracic Oncology Program (Drs. Zheng, Bepler, and Haura) and Biostatistics Core (Dr. Cantor), H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.

Correspondence to: Eric B. Haura, MD, Thoracic Oncology Program, The H. Lee Moffitt Cancer Center and Research Institute, MRC3 East, Room 3056, 12902 Magnolia Drive, Tampa, FL 33612-9497; e-mail: hauraeb@moffitt.usf.edu



Chest. 2005;128(1):308-316. doi:10.1378/chest.128.1.308
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Study objective: Epidermal growth factor receptor (EGFR) signaling has been implicated in the pathogenesis of bronchial dysplasia and overt non-small cell lung cancer (NSCLC). We hypothesized that assaying for EGFR activity using an antibody that recognizes phosphorylated EGFR (pEGFR) may identify a subset of patients whose tumor cells are dependent on EGFR signaling. We also hypothesized that EGFR activity may be prognostic for early-stage NSCLC.

Design: We constructed high-density tissue microarrays using tissues from 193 surgically resected stage I NSCLCs. These arrays were immunostained with a pEGFR antibody, and the intensity of staining was correlated with clinicopathologic variables, as well as disease-free and overall survival (OS). Staining was scored by intensity and the percentage of positively stained tumor cells in triplicate.

Measurements and results: We found the expression of pEGFR (with > 50% of tumor cells staining positive) in 51% of tumor tissues. We found an inverse correlation between pEGFR, and both tumor size and the degree of tobacco smoking. In addition, we found a trend in which pEGFR expression was inversely correlated with disease stage (IA higher than IB). There was no correlation with sex, histology, or disease-free or OS.

Conclusions: Our results suggest that pEGFR levels are present in early-stage NSCLC, especially in patients with small tumors and in those with short smoking histories, but there is no prognostic impact on a patient’s disease course. Targeting EGFR may therefore have more promise in chemoprevention or in patients with smaller early-stage NSCLCs compared with those with more advanced disease.

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