Histology-dependent prognostic role of pERK and p53 protein levels in early-stage non-small cell lung cancer

Abstract

Lung tumors represent a major health problem. In early stage NSCLC tumors, surgical resection is the preferred treatment, but 30-55% of patients will relapse within 5 years after surgery. Thus, the identification of prognostic biomarkers in early stage NSCLC patients, especially those which are therapeutically addressable, is crucial to enhance survival of these patients. We determined the immunohistochemistry expression of key proteins involved in tumorigenesis and oncogenic signaling, p53, EGFR, pAKT and pERK, and correlated their expression level to clinicopathological characteristics and patient outcome. We found EGFR expression is higher in the squamous cell carcinomas than in adenocarcinomas (p=0.043), and that nuclear p53 staining correlated with lower differentiated squamous tumors (p=0.034). Regarding the prognostic potential of the expression of these proteins, high pERK levels proved to be an independent prognostic factor for overall (p<0.001) and progression-free survival (p<0.001) in adenocarcinoma patients, but not in those from the squamous histology, and high p53 nuclear levels were identified as independent prognostic factor for progression-free survival (p=0.031) only in squamous cell carcinoma patients. We propose a role as early prognostic biomarkers for pERK protein levels in adenocarcinoma, and for nuclear p53 levels in squamous cell lung carcinoma. The determination of these potential biomarkers in the adequate histologic context may predict the outcome of early stage NSCLC patients, and may offer a therapeutic opportunity to enhance survival of these patients. ; L.P.A. was funded by Instituto de Salud Carlos III (PI14/01964, PIE15/00076, CB16/12/00442, and R12/0036/0028) and co-funded by the European Union (ERDF/ESF, "Investing in your future"). The laboratory of A.C. was supported by grants from the Spanish Ministry of Economy and Competitiveness (PN I+D+I 2008-2011 and PE I+D+I 2013-2016), Instituto de Salud Carlos III (PI15/00045 and CB16/12/00275) and co-funded by the European Union (ERDF/ESF, "Investing in your future"), Consejeria de Ciencia e Innovacion (CTS-1848) and Consejeria de Salud of the Junta de Andalucia (PI-0096-2014). S.M.P. is funded by Fundación Mutua Madrileña (2014) and Instituto de Salud Carlos III (PI17/00033) and co-funded by the European Union (ERDF/ESF, "Investing in your future"). I.F. is funded by AECC (AIO2015) and Consejería de Igualdad, Salud y Políticas Sociales de la Junta de Andalucía (PI-0029-2013) and Instituto de Salud Carlos III (PI16/01311) and co-funded by the European Union (ERDF/ESF, "Investing in your future"). A.Q. is funded by Instituto de Salud Carlos III (FI12/00429) and co-funded by the European Union (ERDF/ ESF, "Investing in your future"). ; Sí