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...
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| 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 |
| doi_str_mv | 10.1371/journal.pone.0228925 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0228925</identifier><identifier>PMID: 32053675</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenocarcinoma ; Biology and Life Sciences ; Cancer therapies ; Chemotherapy ; Clinical significance ; Critical care ; Deoxyribonucleic acid ; DNA ; Epidermal growth factor ; Epidermal growth factor receptors ; Growth factors ; Internal medicine ; Kim, Sung ; Kinases ; Lung cancer ; Lung diseases ; Medical prognosis ; Medical schools ; Medicine ; Medicine and Health Sciences ; Mortality ; Mutation ; Non-small cell lung carcinoma ; Point mutation ; Prognosis ; Protein-tyrosine kinase ; Signal transduction ; Small cell lung carcinoma ; Studies ; Surgery ; Tyrosine</subject><ispartof>PloS one, 2020-02, Vol.15 (2), p.e0228925-e0228925</ispartof><rights>2020 Yoon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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.</description><subject>Adenocarcinoma</subject><subject>Biology and Life Sciences</subject><subject>Cancer therapies</subject><subject>Chemotherapy</subject><subject>Clinical significance</subject><subject>Critical care</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Epidermal growth factor</subject><subject>Epidermal growth factor receptors</subject><subject>Growth factors</subject><subject>Internal medicine</subject><subject>Kim, Sung</subject><subject>Kinases</subject><subject>Lung cancer</subject><subject>Lung diseases</subject><subject>Medical prognosis</subject><subject>Medical schools</subject><subject>Medicine</subject><subject>Medicine and Health 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significance of EGFR mutation types in lung adenocarcinoma: A multi-centre Korean study</title><author>Yoon, Hee-Young ; Ryu, Jeong-Seon ; Sim, Yun Su ; Kim, Dojin ; Lee, Sung Yong ; Choi, Juwhan ; Park, Sojung ; Ryu, Yon Ju ; Lee, Jin Hwa ; Chang, Jung Hyun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c577t-924ff4a46df83e2e2fb92ffbb3235baf85faef7146c96adfa6d5713d10ae0a993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adenocarcinoma</topic><topic>Biology and Life Sciences</topic><topic>Cancer therapies</topic><topic>Chemotherapy</topic><topic>Clinical significance</topic><topic>Critical care</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Epidermal growth factor</topic><topic>Epidermal growth factor receptors</topic><topic>Growth factors</topic><topic>Internal medicine</topic><topic>Kim, Sung</topic><topic>Kinases</topic><topic>Lung 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One</addtitle><date>2020-02-13</date><risdate>2020</risdate><volume>15</volume><issue>2</issue><spage>e0228925</spage><epage>e0228925</epage><pages>e0228925-e0228925</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>32053675</pmid><doi>10.1371/journal.pone.0228925</doi><orcidid>https://orcid.org/0000-0003-1000-2491</orcidid><orcidid>https://orcid.org/0000-0003-0843-9862</orcidid><orcidid>https://orcid.org/0000-0003-2947-8369</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adenocarcinoma Biology and Life Sciences Cancer therapies Chemotherapy Clinical significance Critical care Deoxyribonucleic acid DNA Epidermal growth factor Epidermal growth factor receptors Growth factors Internal medicine Kim, Sung Kinases Lung cancer Lung diseases Medical prognosis Medical schools Medicine Medicine and Health Sciences Mortality Mutation Non-small cell lung carcinoma Point mutation Prognosis Protein-tyrosine kinase Signal transduction Small cell lung carcinoma Studies Surgery Tyrosine |
| title | Clinical significance of EGFR mutation types in lung adenocarcinoma: A multi-centre Korean study |
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