Immunohistochemical analysis of epidermal growth factor receptor family members in stage I non-small cell lung cancer

Ann Thorac Surg. 2001 Dec;72(6):1868-76. doi: 10.1016/s0003-4975(01)03207-6.


Background: To elucidate the relationship between the expression of epidermal growth factor receptor family members (ErbB-1, neu/ErbB-2, ErbB-3, and ErbB-4) and tumor recurrence.

Methods: We used immunohistochemistry to examine the expression of four epidermal growth factor receptor family members in 73 patients with stage I non-small cell lung cancer.

Results: Using Cox univariate analysis, we determined that angiolymphatic tumor emboli and non-well-differentiated tumor cells were two significant conventional pathologic predictors of tumor recurrence, and that ErbB-1 and ErbB-3 were also significant predictors. Co-expression of ErbB-1+, -3+, or expression of three or more epidermal growth factor receptor family members had a significant effect on lung cancer recurrence. A stepwise multivariate Cox proportional hazards regression analysis provided a predictive model for tumor recurrence.

Conclusions: The present study shows that in patients with a non-well-differentiated tumor, overexpression of ErbB-3 is a useful marker for predicting tumor recurrence. The present study also confirmed that ErbB-1 expression increased in proportion to the loss of tumor differentiation. The correlation between ErbB-3 and distant metastasis was good.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • ErbB Receptors / analysis*
  • Female
  • Humans
  • Lung / pathology
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / pathology*
  • Predictive Value of Tests
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-3 / analysis
  • Receptor, ErbB-4


  • Biomarkers, Tumor
  • ERBB4 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • Receptor, ErbB-4