TY - JOUR
T1 - Prognostic value of KRAS mutations, TP53 mutations and PD-L1 expression among lung adenocarcinomas treated with immunotherapy
AU - Tønnesen, Ea Maria Tønning
AU - Stougaard, Magnus
AU - Meldgaard, Peter
AU - Lade-Keller, Johanne
PY - 2024/1/1
Y1 - 2024/1/1
N2 - 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.
AB - 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.
KW - Antibodies, Monoclonal
KW - IMMUNOHISTOCHEMISTRY
KW - Lung Neoplasms
KW - ONCOGENES
KW - Pathology Department, Hospital
KW - Prognosis
KW - Humans
KW - Proto-Oncogene Proteins p21(ras)/genetics
KW - Adenocarcinoma of Lung/genetics
KW - Tumor Suppressor Protein p53/genetics
KW - Lung Neoplasms/therapy
KW - Carcinoma, Non-Small-Cell Lung/genetics
KW - Immunotherapy
KW - Retrospective Studies
KW - Mutation
KW - B7-H1 Antigen/genetics
UR - http://www.scopus.com/inward/record.url?scp=85144353468&partnerID=8YFLogxK
U2 - 10.1136/jcp-2022-208574
DO - 10.1136/jcp-2022-208574
M3 - Journal article
C2 - 36410939
SN - 0021-9746
VL - 77
SP - 54
EP - 60
JO - Journal of Clinical Pathology
JF - Journal of Clinical Pathology
IS - 1
M1 - 208574
ER -