Synchronous Overexpression of Epidermal Growth Factor Receptor and HER2-neu Protein Is a Predictor of Poor Outcome in Patients with Stage I Non-Small Cell Lung Cancer

Amir Onn, Arlene M. Correa, Michael Gilcrease, Takeshi Isobe, Erminia Massarelli, Corazon D. Bucana, Michael S. O'Reilly, Waun K. Hong, Isaiah J. Fidler, Joe B. Putnam, Roy S. Herbst*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

149 Scopus citations

Abstract

Purpose: Despite maximal therapy, surgically treated patients with stage I non-small cell lung cancer (NSCLC) are at risk for developing metastatic disease. Histopathologic findings cannot adequately predict disease progression, so there is a need to identify molecular factors that serve this purpose. Because the ErbB receptors play an important role in lung cancer progression, we analyzed the expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR, transforming growth factor α (TGFα), and HER2-neu as potential prognostic factors in stage I NSCLC. Experimental Design: Using immunohistochemical techniques, we retrospectively analyzed formalin-fixed, paraffin-embedded samples from 111 patients with resected pathological stage I NSCLC. Then we correlated these data with patient clinical outcome. Results: Median follow-up was 69.3 months. EGFR overexpression (defined as >10% membranous staining) was found in 66 tumors (59.5%). It was significantly more common in T2 tumors than in T1 tumors (P = 0.001), and in more squamous cell carcinomas than in adenocarcinomas (P = 0.07). HER2-neu overexpression was found in 19 tumors (17.1%) and was significantly more common in adenocarcinomas than in squamous cell carcinomas (P = 0.035). Synchronous overexpression of EGFR and HER2-neu was found in 11 tumors (9.9%). Patients with these tumors had a significantly shorter time to recurrence (P = 0.006) and a trend toward shorter overall survival (P = 0.093). Phosphorylated EGFR and transforming growth factor α were detected but were not related to prognosis. Conclusions: Synchronous overexpression of EGFR and HER2-neu at the protein level predicts increased recurrence risk and may predict decreased survival in patients with stage I NSCLC. This suggests that important interactions take place among the different members of the ErbB family during tumor development and suggests a method for choosing targeted therapy. A prospective study is planned.

Original languageEnglish
Pages (from-to)136-143
Number of pages8
JournalClinical Cancer Research
Volume10
Issue number1 I
DOIs
StatePublished - 1 Jan 2004
Externally publishedYes

Funding

FundersFunder number
National Cancer InstituteP50CA070907

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