Combined assessment of EGFR pathway-related molecular markers and prognosis of NSCLC patients

Abstract

The purpose of this study is to evaluate the prognostic value of the combined assessment of multiple molecular markers related to the epidermal growth factor receptor (EGFR) pathway in resected non-small cell lung cancer (NSCLC) patients. Tumour specimens of 178 NSCLC patients were collected and analysed for EGFR and KRAS mutation status by DNA sequencing, and for EGFR copy number by fluorescent in situ hybridisation. Tissue microarrays were generated and used to determine the expression of multiple EGFR pathway-related proteins by immunohistochemistry. We analysed the association between each marker and patient prognosis. Univariate analyses for each clinical variable and each molecular marker were performed using Kaplan -Meier curves and log-rank tests. From these results, we selected the variables KRAS mutations and expression of cytoplasmic EGFR, granular pERK, nuclear pSTAT3, cytoplasmic E-cadherin and cytoplasmic pCMET to enter into a Cox proportional hazards model, along with stage as the strongest clinical variable related with prognosis. Of the EGFR-related markers evaluated here, the markers EGFR, pERK, pSTAT3, E-cadherin, pCMET and mutations in KRAS were associated with survival when analysed in combination in our patient cohort, with P ¼ 0.00015 as the P-value for a test of the additional impact of markers on prognosis, after taking stage into consideration. Confirmation of the impact of these markers in independent studies will be necessary.

Prognostic and predictive values of pERK1/2 and pAkt-1 expression in non-small cell lung cancer patients treated with adjuvant chemotherapy

“…Previous studies have shown that the above markers could not only predict the efficacy of TKI treatment but the prognosis of NSCLC [16][17][18][19]. However, little is known about correlations between the status of these kinases involved in the EGFR pathway and the effectiveness of adjuvant chemotherapy in postoperative NSCLC.…”

Development of [11C]erlotinib Positron Emission Tomography for In Vivo Evaluation of EGF Receptor Mutational Status

“…EGFR protein expression intensity was determined using IHC and scored visually, that is, semiquantitatively, as described previously (19).…”

Efficacy of PHA-848125, a Cyclin-Dependent Kinase Inhibitor, on the K-RasG12DLA2 Lung Adenocarcinoma Transgenic Mouse Model: Evaluation by Multimodality Imaging

“…Alteration of the major regulatory pathways either by gene overexpression or mutation is a frequent event in lung cancer. It is widely accepted that epidermal growth factor receptor (EGFR), K-Ras, and mitogen-activated protein kinase function sequentially in the EGFR signaling pathway and this pathway plays a fundamental role in NSCLC (3,4). K-ras oncogene is frequently mutated in human tumors and activating mutations in K-ras occur in 30% of NSCLC.…”