Clinical significance of EGFR mutation types in lung adenocarcinoma: A multi-centre Korean study.

Adenocarcinoma is the most common type of non-small cell lung cancer. Some causative genomic alterations in epidermal growth factor receptor (EGFR), including deletions in exon 19 (E19 dels) and a point mutation in E21, are known to have favourable prognoses due to sensitivity to tyrosine kinase inh...

Full description

Bibliographic Details
Main Authors: Hee-Young Yoon, Jeong-Seon Ryu, Yun Su Sim, Dojin Kim, Sung Yong Lee, Juwhan Choi, Sojung Park, Yon Ju Ryu, Jin Hwa Lee, Jung Hyun Chang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2020-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0228925
_version_ 1819001916026257408
author Hee-Young Yoon
Jeong-Seon Ryu
Yun Su Sim
Dojin Kim
Sung Yong Lee
Juwhan Choi
Sojung Park
Yon Ju Ryu
Jin Hwa Lee
Jung Hyun Chang
author_facet Hee-Young Yoon
Jeong-Seon Ryu
Yun Su Sim
Dojin Kim
Sung Yong Lee
Juwhan Choi
Sojung Park
Yon Ju Ryu
Jin Hwa Lee
Jung Hyun Chang
author_sort Hee-Young Yoon
collection DOAJ
description Adenocarcinoma is the most common type of non-small cell lung cancer. Some causative genomic alterations in epidermal growth factor receptor (EGFR), including deletions in exon 19 (E19 dels) and a point mutation in E21, are known to have favourable prognoses due to sensitivity to tyrosine kinase inhibitors; however, the prognoses of other uncommon mutations are unclear. This study analysed the clinical significance of EGFR mutation types in lung adenocarcinoma. We retrospectively reviewed 1,020 subjects (mean age: 66.8 years, female: 41.7%) who were diagnosed with advanced lung adenocarcinoma, had EGFR mutation data, and did not undergo surgery from five medical institutes between 2010 and 2016. Subjects were classified according to EGFR mutation status, particularly for exon-specific mutations. EGFR positivity was defined as the presence of mutation and EGFR negativity was defined as wild-type EGFR. EGFR positivity was 38.0%, with the incidence of mutations in E18, E19, E20, and E21 was 3.6%, 51.0%, 3.4%, and 42.0%, respectively. The EGFR positive group survived significantly longer than the negative group (p<0.001), and there was a significant difference in survival among the four EGFR mutation sites (p = 0.003); E19 dels were the only significant factor that lowered mortality (HR: 0.678, p = 0.002), while an E21 mutation was the prognostic factor associated with the most increased mortality (HR: 1.365, p = 0.015). Amongst EGFR positive subjects, the proportion of E19 dels in TKI-responders was significantly higher and that of E21 mutations significantly lower, compared with non-responders. In TKI treatment, mutations in E18 and E20 were not worse factors than the E21 L858R mutation. In conclusion, the presence of EGFR mutations in advanced lung adenocarcinoma can predict a good prognosis; E19 dels prospect to have a better prognosis than other mutations, while an E21 mutation is expected to increase mortality.
first_indexed 2024-12-20T22:56:48Z
format Article
id doaj.art-baadf1d86e57432b91fc29d3f5f1f988
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-20T22:56:48Z
publishDate 2020-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-baadf1d86e57432b91fc29d3f5f1f9882022-12-21T19:24:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01152e022892510.1371/journal.pone.0228925Clinical significance of EGFR mutation types in lung adenocarcinoma: A multi-centre Korean study.Hee-Young YoonJeong-Seon RyuYun Su SimDojin KimSung Yong LeeJuwhan ChoiSojung ParkYon Ju RyuJin Hwa LeeJung Hyun ChangAdenocarcinoma is the most common type of non-small cell lung cancer. Some causative genomic alterations in epidermal growth factor receptor (EGFR), including deletions in exon 19 (E19 dels) and a point mutation in E21, are known to have favourable prognoses due to sensitivity to tyrosine kinase inhibitors; however, the prognoses of other uncommon mutations are unclear. This study analysed the clinical significance of EGFR mutation types in lung adenocarcinoma. We retrospectively reviewed 1,020 subjects (mean age: 66.8 years, female: 41.7%) who were diagnosed with advanced lung adenocarcinoma, had EGFR mutation data, and did not undergo surgery from five medical institutes between 2010 and 2016. Subjects were classified according to EGFR mutation status, particularly for exon-specific mutations. EGFR positivity was defined as the presence of mutation and EGFR negativity was defined as wild-type EGFR. EGFR positivity was 38.0%, with the incidence of mutations in E18, E19, E20, and E21 was 3.6%, 51.0%, 3.4%, and 42.0%, respectively. The EGFR positive group survived significantly longer than the negative group (p<0.001), and there was a significant difference in survival among the four EGFR mutation sites (p = 0.003); E19 dels were the only significant factor that lowered mortality (HR: 0.678, p = 0.002), while an E21 mutation was the prognostic factor associated with the most increased mortality (HR: 1.365, p = 0.015). Amongst EGFR positive subjects, the proportion of E19 dels in TKI-responders was significantly higher and that of E21 mutations significantly lower, compared with non-responders. In TKI treatment, mutations in E18 and E20 were not worse factors than the E21 L858R mutation. In conclusion, the presence of EGFR mutations in advanced lung adenocarcinoma can predict a good prognosis; E19 dels prospect to have a better prognosis than other mutations, while an E21 mutation is expected to increase mortality.https://doi.org/10.1371/journal.pone.0228925
spellingShingle Hee-Young Yoon
Jeong-Seon Ryu
Yun Su Sim
Dojin Kim
Sung Yong Lee
Juwhan Choi
Sojung Park
Yon Ju Ryu
Jin Hwa Lee
Jung Hyun Chang
Clinical significance of EGFR mutation types in lung adenocarcinoma: A multi-centre Korean study.
PLoS ONE
title Clinical significance of EGFR mutation types in lung adenocarcinoma: A multi-centre Korean study.
title_full Clinical significance of EGFR mutation types in lung adenocarcinoma: A multi-centre Korean study.
title_fullStr Clinical significance of EGFR mutation types in lung adenocarcinoma: A multi-centre Korean study.
title_full_unstemmed Clinical significance of EGFR mutation types in lung adenocarcinoma: A multi-centre Korean study.
title_short Clinical significance of EGFR mutation types in lung adenocarcinoma: A multi-centre Korean study.
title_sort clinical significance of egfr mutation types in lung adenocarcinoma a multi centre korean study
url https://doi.org/10.1371/journal.pone.0228925
work_keys_str_mv AT heeyoungyoon clinicalsignificanceofegfrmutationtypesinlungadenocarcinomaamulticentrekoreanstudy
AT jeongseonryu clinicalsignificanceofegfrmutationtypesinlungadenocarcinomaamulticentrekoreanstudy
AT yunsusim clinicalsignificanceofegfrmutationtypesinlungadenocarcinomaamulticentrekoreanstudy
AT dojinkim clinicalsignificanceofegfrmutationtypesinlungadenocarcinomaamulticentrekoreanstudy
AT sungyonglee clinicalsignificanceofegfrmutationtypesinlungadenocarcinomaamulticentrekoreanstudy
AT juwhanchoi clinicalsignificanceofegfrmutationtypesinlungadenocarcinomaamulticentrekoreanstudy
AT sojungpark clinicalsignificanceofegfrmutationtypesinlungadenocarcinomaamulticentrekoreanstudy
AT yonjuryu clinicalsignificanceofegfrmutationtypesinlungadenocarcinomaamulticentrekoreanstudy
AT jinhwalee clinicalsignificanceofegfrmutationtypesinlungadenocarcinomaamulticentrekoreanstudy
AT junghyunchang clinicalsignificanceofegfrmutationtypesinlungadenocarcinomaamulticentrekoreanstudy