TY - JOUR
T1 - Expression of the receptor tyrosine kinase EphA2 is increased in smokers and predicts poor survival in non -small cell lung cancer
AU - Brannan, Jennifer M.
AU - Dong, Wenli
AU - Prudkin, Ludmila
AU - Behrens, Carmen
AU - Lotan, Reuben
AU - Bekele, B. Nebiyou
AU - Wistuba, Ignacio
AU - Johnson, Fayem
PY - 2009/7/1
Y1 - 2009/7/1
N2 - Purpose: Up-regulation of the receptor tyrosine kinase EphA2 has been shown in several epithelial cancers. Epidermal growth factor receptor (EGFR) and K-Ras have been reported to regulate EphA2 in several in vitro models, but this regulation has never been examined in tumors frompatients.Because of the establishedimportance of EGFRand K-Rasmutations innon - small cell lung cancer (NSCLC), we investigated the relationship between these mutations and EphA2 in this cancer type. The significance of EphA2 expression was further examined by testing for correlation with other clinical parameters. Experimental Design: EphA2 expression was analyzed by immunohistochemistry in tissue microarray format using surgically resected NSCLC specimens (n = 279). EGFR and K-Ras mutation status was determined formost specimens.The correlation between EphA2 expression and EGFR or K-Ras mutation status was examined, along with several clinicopathologic variables of the tumors. The effects of increasing EGFR and K-Ras activity on EphA2 expression and activity were examined in two cell lines. Results: EphA2 expression was detected in >90% of tumor samples. Expression of EphA2 was positively correlated with activated EGFR but not with EGFR mutations. EphA2 expression was increased in patients harboring K-Ras mutations. EphA2 expression was positively correlated with a history of smoking, and high EphA2 scores predicted poorer progression-free and overall survivals. Conclusions: EphA2 expression in NSCLCis associatedwith K-Rasmutations, EGFRactivation, smoking history, and poor prognosis. EphA2 expression is up-regulated in the context of EGFRor K-Ras activation. The potential of EphA2 as a therapeutic target for NSCLC should be further investigated.
AB - Purpose: Up-regulation of the receptor tyrosine kinase EphA2 has been shown in several epithelial cancers. Epidermal growth factor receptor (EGFR) and K-Ras have been reported to regulate EphA2 in several in vitro models, but this regulation has never been examined in tumors frompatients.Because of the establishedimportance of EGFRand K-Rasmutations innon - small cell lung cancer (NSCLC), we investigated the relationship between these mutations and EphA2 in this cancer type. The significance of EphA2 expression was further examined by testing for correlation with other clinical parameters. Experimental Design: EphA2 expression was analyzed by immunohistochemistry in tissue microarray format using surgically resected NSCLC specimens (n = 279). EGFR and K-Ras mutation status was determined formost specimens.The correlation between EphA2 expression and EGFR or K-Ras mutation status was examined, along with several clinicopathologic variables of the tumors. The effects of increasing EGFR and K-Ras activity on EphA2 expression and activity were examined in two cell lines. Results: EphA2 expression was detected in >90% of tumor samples. Expression of EphA2 was positively correlated with activated EGFR but not with EGFR mutations. EphA2 expression was increased in patients harboring K-Ras mutations. EphA2 expression was positively correlated with a history of smoking, and high EphA2 scores predicted poorer progression-free and overall survivals. Conclusions: EphA2 expression in NSCLCis associatedwith K-Rasmutations, EGFRactivation, smoking history, and poor prognosis. EphA2 expression is up-regulated in the context of EGFRor K-Ras activation. The potential of EphA2 as a therapeutic target for NSCLC should be further investigated.
UR - http://www.scopus.com/inward/record.url?scp=67650403368&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67650403368&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-09-0473
DO - 10.1158/1078-0432.CCR-09-0473
M3 - Article
C2 - 19531623
AN - SCOPUS:67650403368
SN - 1078-0432
VL - 15
SP - 4423
EP - 4430
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 13
ER -