Analysis of the p38MAPK pathway in the prognosis of patients with surgically resected stage I-II NSCLC

Abstract only e18513 Background: TNM staging is the most important prognostic factor in Non-Small Cell Lung Cancer (NSCLC). The MAPK pathway, including p38, JNK and ERK, has been slightly studied in NSCLC, with controversial prognostic significance. Methods: The records of 211 patients with stage I-...

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Published in:	Journal of clinical oncology Vol. 31; no. 15_suppl; p. e18513
Main Authors:	Pardo-Coto, Pablo, Esteban, Emilio, Astudillo, Aurora, Gracia, Jose Manuel, Corral, Norberto, Izquierdo Manuel, Marta, Lopez, Carolina Muriel, Sanmamed, Miguel F., Gutierrez Restrepo, Eduardo, Valle Pereda, Miguel, Alvarez Fernandez, Carlos, Pérez Arnillas, Quionia, Berros Fombella, Jose Pablo, Jiménez, Paula, Vieitez de Prado, Jose Maria, Fra, Joaquin
Format:	Journal Article
Language:	English
Published:	20-05-2013
Online Access:	Get full text
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Summary:	Abstract only e18513 Background: TNM staging is the most important prognostic factor in Non-Small Cell Lung Cancer (NSCLC). The MAPK pathway, including p38, JNK and ERK, has been slightly studied in NSCLC, with controversial prognostic significance. Methods: The records of 211 patients with stage I-II NSCLC, surgically resected at Asturias University Hospital between 2000 and 2004 were retrospectively reviewed. Formalin-fixed, paraffin-embedded histological tumour specimens were used to construct tissue microarrays. The nuclear level of phosphorilated p38alpha (nP-p38), JNK (nP-JNK) and ERK (nP-ERK) was assessed using inmunohistochemistry (IHC). Phosphorilated protein expression was considered positive if the staining was present in at least 100% of the nucleus studied. EGFR was also analyzed with IHC following previous studies and was considered positive (EGFR+) if staining was observed in >10% of the cells. Clinicopahological data and outcome differences in terms of overall survival (OS) were compared between positive and negative patients. Results: Patients with nP+ for p38, JNK or ERK had a trend to better OS than those respectively negative for each protein (HR=0.68, p=0.14; HR= 0.75, p=0.16; HR=0.64, p=0.14), and the difference was significative for nP-p38+ in adenocarcinoma histology (p=0.012). EGFR+ patients had worse OS than EGFR- (HR=1.59, p=0.02), but in nP-p38+ patients, those with EGFR+ tumors had similar survival than EGFR- (p=0.9). Fifteen patients were positive for the three MAPK (MAPK “Triple Positive”, MTP), and had better OS than the rest not MTP (HR=0.20, p=0.01). In the univariant analysis, stage, histologic grade, surgery (pneumonectomy vs lobectomy), EGFR status and MTP had significant influence on OS. Multivariant analysis only confirmed the stage as an independent factor (p=0.01). Conclusions: TNM staging remains the most important factor in the prognosis of NSCLC. The activation of the MAPK pathway, its interaction with EGFR, and the MTP feature might have prognostic influence in this tumor and warrant confirmation in a large prospective trial. The potential therapeutic implications of pharmacological manipulation of the MAPK pathway highlight the importance of this study.
ISSN:	0732-183X 1527-7755
DOI:	10.1200/jco.2013.31.15_suppl.e18513