KRAS Mutations in Advanced Nonsquamous Non-Small-Cell Lung Cancer Patients Treated with First-Line Platinum-Based Chemotherapy Have No Predictive Value

Background:Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation is thought to be related with dismal outcome for non–small-cell lung cancer (NSCLC) patients. The role of KRAS mutation as a predictor of response to chemotherapy for patients with metastatic NSCLC is poorly understood.Methods:From a retrospective database of two university hospitals, all patients with advanced, nonsquamous NSCLC treated with first-line platinum-containing chemotherapy were selected. Mutation analysis for KRAS was performed and the relation with response to chemotherapy was assessed. Secondary endpoints were its relation with response to progression-free survival (PFS) and overall survival (OS).Results:A total of 161 patients, 94 men and 67 women, were included in this study. Median age was 60 years. The majority of patients (79%) had stage IV disease, of which 60 patients (37%) had a KRAS mutation. Patients with a KRAS mutation had a similar response to treatment as patients with KRAS wild-type (wt) (p = 0.77). Median PFS in KRAS-mutated patients was 4.0 months versus 4.5 months in KRAS wt patients (hazard ratio = 1.3; [95% confidence interval, 0.9–1.8]; p = 0.16). Median OS in patients with KRAS mutation was 7.0 months versus 9.3 months in patients with KRAS wt (hazard ratio = 1.2; [95% confidence interval, 0.9–1.7]; p = 0.25). Type of KRAS mutation had no influence on response or outcome.Conclusion:On the basis of our multicenter data presented here, we conclude that KRAS mutation is not predictive for worse response to chemotherapy, PFS, and OS in advanced NSCLC patients treated with platinum-based chemotherapy in first-line setting

Correlation of immunohistochemical staining p63 and TTF-1 with EGFR and K-ras mutational spectrum and diagnostic reproducibility in non small cell lung carcinoma

For treatment purposes, distinction between squamous cell carcinoma and adenocarcinoma is important. The aim of this study is to examine the diagnostic accuracy on lung cancer small biopsies for the distinction between adenocarcinoma and squamous cell carcinoma and relate these to immunohistochemical and KRAS and EGFR mutation analysis. An interobserver study was performed on 110 prospectively collected biopsies obtained by bronchoscopy or transthoracic needle biopsy of patients with non-small cell lung cancer. The diagnosis was correlated with immunohistochemical (IHC) analysis for markers of adeno- (TTF1 and/or mucin positivity) and squamous cell differentiation (P63 and CK5/6) as well as KRAS and EGFR mutation analysis. Eleven observers independently read H&E-stained slides of 110 cases, resulting in a kappa value of 0.55 ± 0.10. The diagnosis non-small cell lung cancer not otherwise specified was given on average on 29.5 % of the biopsies. A high concordance was observed between hematoxylin-eosin-based consensus diagnosis (≥8/11 readings concordant) and IHC markers. In all cases with EGFR (n = 1) and KRAS (n = 20) mutations, adenodifferentiation as determined by IHC was present and p63 staining was absent. In 2 of 25 cases with a consensus diagnosis of squamous cell carcinoma, additional stainings favored adenodifferentation, and a KRAS mutation was present. P63 is most useful for distinction between EGFR/KRAS mutation positive and negative patients. In the diagnostic work-up of non-small cell lung carcinoma the limited reproducibility on small biopsies is optimized with immunohistochemical analysis, resulting in reliable delineation for predictive analysis