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.
Zheng
Zhong
Z
Thoracic Oncology Program, The H. Lee Moffitt Cancer Center and Research Institute, MRC3 East, Room 3056, 12902 Magnolia Drive, Tampa, FL 33612-9497, USA.
Bepler
Gerold
G
Cantor
Alan
A
Haura
Eric B
EB
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