TY - JOUR
T1 - High tumor mutation burden predicts favorable outcome among patients with aggressive histological subtypes of lung adenocarcinoma
T2 - A population-based single-institution study
AU - Talvitie, Eva Maria
AU - Vilhonen, Heikki
AU - Kurki, Samu
AU - Karlsson, Antti
AU - Orte, Katri
AU - Almangush, Alhadi
AU - Mohamed, Hesham
AU - Liljeroos, Lassi
AU - Singh, Yajuvinder
AU - Leivo, Ilmo
AU - Laitinen, Tarja
AU - Kallajoki, Markku
AU - Taimen, Pekka
N1 - Funding Information:
This study was conducted in collaboration with Auria Biobank. We would like to thank the personnel of Auria Biobank for their help with histology and slide scanning. Additionally, we thank the Academy of Finland Clinical Researcher funding for supporting PT and the Finnish Cancer Foundation for supporting PT and IL.
Funding Information:
This study was supported by ERVA funding from the Hospital District of Southwest Finland (ET, HV), Eka Grant from The Finnish Medical Foundation (HV) and Roche Finland.
Publisher Copyright:
© 2020 The Authors
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/9
Y1 - 2020/9
N2 - Objectives: Tumor mutation burden (TMB) is an emerging predictive cancer biomarker. Few studies have addressed the prognostic role of TMB in non-small cell lung carcinoma, with conflicting results. Moreover, the association of TMB with different histological subtypes of lung adenocarcinoma has hitherto not been systematically evaluated. Here we studied the prognostic value of TMB and its distribution in different histological subtypes of lung adenocarcinomas in a retrospective cohort using the most recent updated classification guidelines. Materials and methods: 176 surgically resected stage I–IV lung adenocarcinomas were histologically reclassified according to WHO 2015 guidelines. A modified classification subdividing the acinar subtype into classic acinar, complex glandular and cribriform subtypes was further applied and potentially prognostic histopathological characteristics such as tumor-infiltrating lymphocytes were evaluated. 148 patients with stage I–III tumors and complete follow-up data were included in the survival analyses. TMB was determined by a commercial next generation sequencing panel from 131 tumors, out of which 105 had survival data available. Results: Predominant micropapillary, solid and complex glandular as well as nonpredominant cribriform histological subtypes were associated with significantly shorter survival. High TMB concentrated in micropapillary, solid and acinar predominant subtypes. Interestingly, TMB ≥ 14 mutations/MB conferred a stage- and histology-independent survival benefit compared to TMB < 14 in multivariable analysis for overall (HR 0.284, 95% CI 0.14–0.59, P=0.001) and disease-specific survival (HR 0.213, 95% CI 0.08–0.56, P=0.002). Conclusion: TMB was an independent biomarker of favorable prognosis in our cohort of lung adenocarcinoma despite being associated with predominant histological subtypes considered aggressive.
AB - Objectives: Tumor mutation burden (TMB) is an emerging predictive cancer biomarker. Few studies have addressed the prognostic role of TMB in non-small cell lung carcinoma, with conflicting results. Moreover, the association of TMB with different histological subtypes of lung adenocarcinoma has hitherto not been systematically evaluated. Here we studied the prognostic value of TMB and its distribution in different histological subtypes of lung adenocarcinomas in a retrospective cohort using the most recent updated classification guidelines. Materials and methods: 176 surgically resected stage I–IV lung adenocarcinomas were histologically reclassified according to WHO 2015 guidelines. A modified classification subdividing the acinar subtype into classic acinar, complex glandular and cribriform subtypes was further applied and potentially prognostic histopathological characteristics such as tumor-infiltrating lymphocytes were evaluated. 148 patients with stage I–III tumors and complete follow-up data were included in the survival analyses. TMB was determined by a commercial next generation sequencing panel from 131 tumors, out of which 105 had survival data available. Results: Predominant micropapillary, solid and complex glandular as well as nonpredominant cribriform histological subtypes were associated with significantly shorter survival. High TMB concentrated in micropapillary, solid and acinar predominant subtypes. Interestingly, TMB ≥ 14 mutations/MB conferred a stage- and histology-independent survival benefit compared to TMB < 14 in multivariable analysis for overall (HR 0.284, 95% CI 0.14–0.59, P=0.001) and disease-specific survival (HR 0.213, 95% CI 0.08–0.56, P=0.002). Conclusion: TMB was an independent biomarker of favorable prognosis in our cohort of lung adenocarcinoma despite being associated with predominant histological subtypes considered aggressive.
KW - Histological subtype
KW - Lung adenocarcinoma
KW - Non-small cell lung cancer
KW - Prognostic biomarker
KW - Tumor mutation burden
U2 - 10.1016/j.neo.2020.05.004
DO - 10.1016/j.neo.2020.05.004
M3 - Article
C2 - 32585428
AN - SCOPUS:85086732864
VL - 22
SP - 333
EP - 342
JO - NeoPlasia
JF - NeoPlasia
SN - 1522-8002
IS - 9
ER -
