Prognostic value ofKRASmutations,TP53mutations and PD-L1 expression among lung adenocarcinomas treated with immunotherapy
- 21 November 2022
- journal article
- research article
- Published by BMJ in Journal of Clinical Pathology
- Vol. 77 (1), 54-60
- https://doi.org/10.1136/jcp-2022-208574
Abstract
Aims The aim of this study was to investigate the association between oncogenic alterations and programmed cell death ligand 1 (PD-L1) expression in lung adenocarcinomas, as well as the prognostic value of KRAS and/or TP53 mutations in patients treated with immunotherapy. Methods This study is a retrospective cohort study of 519 patients with lung adenocarcinomas analysed for mutations and PD-L1 expression. Data were collected from electronic pathology record system, next-generation sequencing system, and clinical databases. Association between mutations and PD-L1 expression was investigated, as well as survival statistics of the 65 patients treated with immunotherapy. Results 41% of the samples contained a KRAS mutation, predominantly together with mutations in TP53 (41%) or STK11 (10%). Higher expression of PD-L1 was seen among patients with KRAS mutations (p=0.002) and EGFR wild type (p=0.006). For patients treated with immunotherapy, there was no statistically significant difference for overall survival (OS) and progression-free survival (PFS) according to KRAS mutation status, TP53 mutation status or PD-L1 expression. The HR for concomitant mutations in TP53 and KRAS was 0.78 (95% CI 0.62 to 0.99) for OS and 0.43 (0.21 to 0.88) for PFS. Furthermore, concomitant TP53 and KRAS mutations predicted a better PFS (p=0.015) and OS (p=0.029) compared with no mutations or a single mutation in either TP53 or KRAS. Conclusion Mutations in TP53 together with KRAS may serve as a potential biomarker for survival benefits with immunotherapy.Keywords
This publication has 56 references indexed in Scilit:
- PD-L1 expression as predictive biomarker in patients with NSCLC: a pooled analysisOncotarget, 2016
- PD-L1 Expression and Survival among Patients with Advanced Non–Small Cell Lung Cancer Treated with ChemotherapyTranslational Oncology, 2016
- KRAS mutation is a weak, but valid predictor for poor prognosis and treatment outcomes in NSCLC: A meta-analysis of 41 studiesOncotarget, 2016
- Expression of PD-1 and Its Ligands, PD-L1 and PD-L2, in Smokers and Never Smokers with KRAS-Mutant Lung CancerJournal of Thoracic Oncology, 2015
- The 2015 World Health Organization Classification of Lung TumorsJournal of Thoracic Oncology, 2015
- Co-occurring Genomic Alterations Define Major Subsets of KRAS-Mutant Lung Adenocarcinoma with Distinct Biology, Immune Profiles, and Therapeutic VulnerabilitiesCancer Discovery, 2015
- Differential Activity of Nivolumab, Pembrolizumab and MPDL3280A according to the Tumor Expression of Programmed Death-Ligand-1 (PD-L1): Sensitivity Analysis of Trials in Melanoma, Lung and Genitourinary CancersPLOS ONE, 2015
- The prevalence of EGFR mutations in non‐small cell lung cancer in an unselected Caucasian populationAPMIS, 2014
- The frequency of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC): routine screening data for central Europe from a cohort studyBMJ Open, 2013
- Molecular Epidemiology of EGFR and KRAS Mutations in 3,026 Lung Adenocarcinomas: Higher Susceptibility of Women to Smoking-Related KRAS-Mutant CancersClinical Cancer Research, 2012