title: 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=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.
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: M I
authors.initials: MI
authors.lastname: Galleges Ruiz
authors.forename: K
authors.initials: K
authors.lastname: Floor
authors.forename: S M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: K
authors.initials: K
authors.lastname: Grünberg
authors.forename: F B J M
authors.initials: FB
authors.lastname: Thunnissen
authors.forename: J A M
authors.initials: JA
authors.lastname: Belien
authors.forename: G A
authors.initials: GA
authors.lastname: Meijer
authors.forename: G J
authors.initials: GJ
authors.lastname: Peters
authors.forename: E F
authors.initials: EF
authors.lastname: Smit
authors.forename: J A
authors.initials: JA
authors.lastname: Rodriguez
authors.forename: G
authors.initials: G
authors.lastname: Giaccone
mesh_terms: D015820:Cadherins / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality*; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D005260:Female; D018628:Gene Dosage; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality*; D008297:Male; D015999:Multivariate Analysis; D009154:Mutation; D011379:Prognosis; D050796:STAT3 Transcription Factor / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D015820:Cadherins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D066246:ErbB Receptors