Activation state EGFR and STAT-3 as prognostic markers in resected non-small cell lung cancer

Lung Cancer. 2007 Mar;55(3):349-55. doi: 10.1016/j.lungcan.2006.11.003. Epub 2006 Dec 8.


Background: Total EGFR expression by immunohistochemistry (IHC) has failed to demonstrate prognostic importance. We hypothesized that activation (phosphorylated) state of EGFR (p-EGFR) and its activated downstream signal pathway (p-STAT-3) will have prognostic value in NSCLC.

Methods: 145 patients underwent lung resection for NSCLC at University Hospitals from 1998-2002. A database with TNM stage, gender, age, time to recurrence, and survival was established. p-EGFR and p-STAT-3 levels were quantified by IHC. Specimens were divided into negative, 1+, 2+, or 3+ (5-19%, 20-50%, >50% of tumor cells staining respectively). Cox proportional hazard model was used for multivariate analysis.

Results: Median age was 70 years. 58% were female and 54% had adenocarcinoma. Pathologic stage was as follows: stage I: 54%, stage II: 31%, stage III: 15%. 32% were positive for p-EGFR (squamous 36%, adenocarcinoma 29%). p-STAT-3 staining was seen in 38% and was higher in adenocarcinoma (46%) versus squamous cell (27%, p=0.02) and was higher in patients >70 years than compared to those <70 years (p=0.06). There was a trend toward co-expression of p-EGFR and p-STAT-3 (p=0.09). The 5-year Kaplan-Meier probabilities of overall survival were not different amongst patients with activated versus no activation of EGFR and STAT-3.

Conclusions: Although EGFR is commonly expressed in NSCLC ( approximately 70%), p-EGFR is seen in only 1/3 of patients. p-EGFR and p-STAT-3 were commonly co-expressed in tumors compatible with known signal transduction pathways in lung cancer. However, EGFR and STAT-3 activation status does not provide prognostic information in resected disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • ErbB Receptors / metabolism*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / metabolism*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Phosphorylation
  • Prognosis
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / physiology


  • Biomarkers, Tumor
  • STAT3 Transcription Factor
  • ErbB Receptors