Histology-dependent prognostic role of pERK and p53 protein levels in early-stage non-small cell lung cancer
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Álvaro Quintanal-Villalonga1, Mariló Mediano2,3, Irene Ferrer1,6, Ricardo Meléndez2, Andrés Carranza-Carranza2,3, Rocío Suárez1, Amancio Carnero2, Sonia Molina-Pinelo2,6,* and Luis Paz-Ares1,4,5,6,*
1H120-CNIO Lung Cancer Clinical Research Unit, Instituto de Investigación 12 de Octubre and CNIO, Madrid, Spain
2Instituto de Biomedicina de Sevilla (IBIS) (HUVR, CSIC, Universidad de Sevilla), Sevilla, Spain
3Hospital Universitario Virgen del Rocío (HUVR), Sevilla, Spain
4Medical Oncology Department, Hospital Universitario Doce de Octubre & Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain
5Medical School, Universidad Complutense, Madrid, Spain
6CiberOnc, Madrid, Spain
*These authors have contributed equally to this work
Luis Paz-Ares, email: [email protected]
Sonia Molina-Pinelo, email: [email protected]
Keywords: p53; pERK; prognostic; biomarkers; NSCLC
Received: December 06, 2017 Accepted: March 11, 2018 Published: April 13, 2018
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.
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