Immunohistochemical validation study of 15-gene biomarker panel predictive of benefit from adjuvant chemotherapy in resected non-small-cell lung cancer: analysis of JBR.10

ObjectiveThere are no validated approaches to predict benefit from adjuvant chemotherapy for resected patients with non-small-cell lung cancer (NSCLC). The aim of this study was to translate a 15-gene mRNA expression profile published by Zhu et al, shown to be prognostic and predictive of benefit, into a readily applicable immunohistochemistry (IHC) panel.MethodsFor seven of the genes in the gene expression profile (GEP) for which suitable commercial antibodies were available, we semiquantitatively assessed the IHC expression and prognostic significance for 173 patients treated at the Saint John Regional Hospital (SJRH). Cut-offs for high and low expression were defined for each marker and applied to IHC scores from 291 of the 482 patients in JBR.10, including patients on both the adjuvant chemotherapy and observation arms. The prognostic and predictive value of these markers on overall survival (OS) or recurrence-free survival (RFS) was assessed by Cox regression models.ResultsIn the SJRH cohort, in 62 patients with resected stage II–III NSCLC, the prognostic significance of IHC assays for four proteins were concordant with Zhu’s GEP results. Low FOSL2 (OS, HR=0.15; p=0.0001; RFS, HR=0.14; p