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Lung Cancer. 2007 Mar;55(3):349-55. Epub 2006 Dec 8.

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

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From the Department of Medicine, Divisions of Hematology/Oncology, Case Comprehensive Cancer Center, Case Western Reserve University and University Hospitals of Cleveland, OH 44106, United States.



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.


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.


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.


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.

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