{Reference Type}: Journal Article
{Title}: Prognostic value of KRAS mutations, TP53 mutations and PD-L1 expression among lung adenocarcinomas treated with immunotherapy.
{Author}: Tønnesen EMT;Stougaard M;Meldgaard P;Lade-Keller J;
{Journal}: J Clin Pathol
{Volume}: 77
{Issue}: 1
{Year}: Dec 2023 14
{Factor}: 4.463
{DOI}: 10.1136/jcp-2022-208574
{Abstract}: <B>OBJECTIVE: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>Mutations in TP53 together with KRAS may serve as a potential biomarker for survival benefits with immunotherapy.