Clinicopathologic characteristics of EGFR, KRAS, and ALK alterations in 6,595 lung cancers

Boram Lee, Taebum Lee, Se-Hoon Lee, Yoon La Choi, Joungho Han, Boram Lee, Taebum Lee, Se-Hoon Lee, Yoon La Choi, Joungho Han

Abstract

Background: EGFR, KRAS, and ALK alterations are major genetic changes found in non-small cell lung cancers (NSCLCs). Testing advanced lung adenocarcinoma tumors for these three genes is now standard care. The purpose of this study was to investigate the clinicopathologic expression pattern of these three genes in East Asian NSCLC patients.

Patients and methods: We conducted a retrospective study of all patients tested for mutations of these three genes at a single institute in Korea between 2006 and 2014. Study data were extracted from electronic medical records. Univariate and multivariate logistic regression analyses were used to measure associations between clinicopathologic features and alterations of EGFR, KRAS, and ALK.

Results: We detected 12 EGFR-mutated tumors with additional mutations in KRAS (N=6, 0.1%) or ALK (N=6, 0.1%). General clinicopathologic characteristics of tumors with EGFR, KRAS, or ALK mutations were similar to previous reports. Patients having EGFR L858R point mutations were older than patients having EGFR exon 19 deletions. EGFR G719X point mutations were more common in men and smokers than exon 19 deletions or L858R point mutations. Tumors having KRAS G12C mutations were less often of mucinous type than those with G12D or G12V, mutations.

Conclusions: This is the largest three gene molecular epidemiology study in East Asian NSCLC patients. Each genetic alteration was associated with distinct clinicopathologic characteristics. Furthermore, different age and sex are associated with different subtypes of EGFR and KRAS mutations.

Keywords: ALK; EGFR; KRAS; lung cancer; molecular epidemiology.

Conflict of interest statement

The authors declare no conflicts of interest with regard to the present paper.

Figures

Figure 1. Comparison between exon 19 deletion…
Figure 1. Comparison between exon 19 deletion and L858R point mutation
Deletions in exon 19 are frequent in younger patients and L858R mutations are frequent in older ages.
Figure 2. The proportion and subtypes of…
Figure 2. The proportion and subtypes of EGFR mutation
A. Sex proportion and subtypes of EGFR mutation. Deletion in exon 19 and L858R appears more often in women. However, G719X and S768I do not have this tendency. B. Proportion of smokers and subtypes of EGFR mutation. The trend is similar to the sex proportion. E19: deletion in exon 19, E20: insertion in exon 20.
Figure 3. Comparison of proportion of mucinous…
Figure 3. Comparison of proportion of mucinous type between subtypes of KRAS mutation
Proportion of mucinous type is higher in G12D and G12V subtypes than G12C subtype.

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