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Aberrant Signaling through the HER2-ERK1/2 Pathway is Predictive of Reduced Disease-Free and Overall Survival in Early Stage Non-Small Cell Lung Cancer (NSCLC) Patients.

ABSTRACT: Background: Purpose of this study was to evaluate the contribution of the Extracellular-regulated protein kinase (ERK)-1/2 pathway to oncogenic signaling elicited by the tyrosine kinase receptor HER2 in Non-Small Cell Lung Cancer (NSCLC) and to assess the prognostic value of these oncoproteins in NSCLC patients. Methods: Immunohistochemistry was performed to determine expression and activation of HER2 and ERK1/2 (detected by phosphorylation of Y1248 and T202/Y204, respectively) using Tissue Micro Arrays (TMA) containing matched normal and neoplastic tissues from 132 NSCLC patients. Survival analysis was carried out using the Kaplan-Meier method. Univariate and multivariate analysis were used to evaluate the prognostic value of pERK1/2, pHER2 and a combination thereof with clinical-pathological parameters such as age, lymph node status (N), size (T), stage (TNM) and grade. Results: We found that HER2 was overexpressed in 33/120 (27%) and activated in 41/114 (36%) cases; ERK1/2 was activated in 44/102 (43%) cases. A direct association was found between pERK1/2 and pHER2 (23/41; p=0.038). In addition, patients positive for pERK1/2 and for both pHER2 and pERK1/2 showed significantly worse overall survival (OS) and disease-free survival (DFS) compared with negative patients. Univariate and multivariate analysis of patients' survival revealed that positivity for pHER2-pERK1/2 and for pERK1/2 alone were independent prognostic factors of poor survival in NSCLC patients. In particular, this association was significantly important for DFS in stage I+II patients. Conclusion: This study provides evidence that activated ERK1/2 and/or the combined activation of HER2 and ERK1/2 are good indicators of poor prognosis in NSCLC patients, not only in unselected patients but also in early stage disease.

SUBMITTER: Scrima M

PROVIDER: S-EPMC5327372 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Aberrant Signaling through the HER2-ERK1/2 Pathway is Predictive of Reduced Disease-Free and Overall Survival in Early Stage Non-Small Cell Lung Cancer (NSCLC) Patients.

Scrima Marianna M Zito Marino Federica F Oliveira Duarte Mendes DM Marinaro Cinzia C La Mantia Elvira E Rocco Gaetano G De Marco Carmela C Malanga Donatella D De Rosa Nicla N Rizzuto Antonia A Botti Gerardo G Franco Renato R Zoppoli Pietro P Viglietto Giuseppe G

Journal of Cancer 20170115 2

<b>Background:</b> Purpose of this study was to evaluate the contribution of the Extracellular-regulated protein kinase (ERK)-1/2 pathway to oncogenic signaling elicited by the tyrosine kinase receptor HER2 in Non-Small Cell Lung Cancer (NSCLC) and to assess the prognostic value of these oncoproteins in NSCLC patients. <b>Methods:</b> Immunohistochemistry was performed to determine expression and activation of HER2 and ERK1/2 (detected by phosphorylation of Y1248 and T202/Y204, respectively) usi ...[more]

PMID: 28243327

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Dataset Information

Aberrant Signaling through the HER2-ERK1/2 Pathway is Predictive of Reduced Disease-Free and Overall Survival in Early Stage Non-Small Cell Lung Cancer (NSCLC) Patients.

Publications

Aberrant Signaling through the HER2-ERK1/2 Pathway is Predictive of Reduced Disease-Free and Overall Survival in Early Stage Non-Small Cell Lung Cancer (NSCLC) Patients.

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