Nuclear EGFR protein expression predicts poor survival in early stage non-small cell lung cancer

Lung Cancer. 2013 Jul;81(1):138-41. doi: 10.1016/j.lungcan.2013.03.020. Epub 2013 Apr 28.

Abstract

Introduction: Nuclear EGFR (nEGFR) has been identified in various human tumor tissues, including cancers of the breast, ovary, oropharynx, and esophagus, and has predicted poor patient outcomes. We sought to determine if protein expression of nEGFR is prognostic in early stage non-small cell lung cancer (NSCLC).

Methods: Resected stages I and II NSCLC specimens were evaluated for nEGFR protein expression using immunohistochemistry (IHC). Cases with at least one replicate core containing ≥5% of tumor cells demonstrating strong dot-like nucleolar EGFR expression were scored as nEGFR positive.

Results: Twenty-three (26.1% of the population) of 88 resected specimens stained positively for nEGFR. Nuclear EGFR protein expression was associated with higher disease stage (45.5% of stage II vs. 14.5% of stage I; p = 0.023), histology (41.7% in squamous cell carcinoma vs. 17.1% in adenocarcinoma; p = 0.028), shorter progression-free survival (PFS) (median PFS 8.7 months [95% CI 5.1-10.7 mo] for nEGFR positive vs. 14.5 months [95% CI 9.5-17.4 mo] for nEGFR negative; hazard ratio (HR) of 1.89 [95% CI 1.15-3.10]; p = 0.011), and shorter overall survival (OS) (median OS 14.1 months [95% CI 10.3-22.7 mo] for nEGFR positive vs. 23.4 months [95% CI 20.1-29.4 mo] for nEGFR negative; HR of 1.83 [95% CI 1.12-2.99]; p = 0.014).

Conclusions: Expression of nEGFR protein was associated with higher stage and squamous cell histology, and predicted shorter PFS and OS, in this patient cohort. Nuclear EGFR serves as a useful independent prognostic variable and as a potential therapeutic target in NSCLC.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Cell Nucleus / metabolism
  • Disease-Free Survival
  • ErbB Receptors / metabolism*
  • Female
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Retrospective Studies

Substances

  • Biomarkers, Tumor
  • EGFR protein, human
  • ErbB Receptors