Activation state EGFR and STAT-3 as prognostic markers in resected non-small cell lung cancer.
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.
Cortas
Tania
T
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.
Eisenberg
Rosana
R
Fu
Pingfu
P
Kern
Jeffrey
J
Patrick
Lauren
L
Dowlati
Afshin
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010766:Phosphorylation; D011379:Prognosis; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D014408:Biomarkers, Tumor; D050796:STAT3 Transcription Factor; D066246:ErbB Receptors