Small tumor size and limited smoking history predicts activated epidermal growth factor receptor in early-stage non-small cell lung cancer.
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.


METHODS
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.


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.
Thoracic Oncology Program, The H. Lee Moffitt Cancer Center and Research Institute, MRC3 East, Room 3056, 12902 Magnolia Drive, Tampa, FL 33612-9497, USA.
Zhong
Z
Zheng
Gerold
G
Bepler
Alan
A
Cantor
Eric B
EB
Haura
D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D046228:Microarray Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D012907:Smoking / Q000009:adverse effects*; D013194:Staining and Labeling; D018709:Statistics, Nonparametric
D066246:ErbB Receptors