The effective mutation of epidermal growth factor receptor in synchronous multiple primary lung cancers: study of clinical, radiographic and pathological factors

Abstract

Objective: To investigate the clinical, pathological and CT features associated with the effective mutation of epidermal growth factor receptor (EGFR) in multiple primary lung cancers (MPLCs) , and to determine the target population of EGFR mutations tests. Methods: A total of 558 nodules from 232 patients with MPLCs who underwent surgery in the Cancer Hospital of Chinese Academy of Medical Sciences from August 2017 to December 2017 were selected. Two hundreds and sixteen nodules were detected by DNA direct sequencing. Chi-square test and Mann-Whitney U test were used to compare the clinical, pathological and CT features of 216 nodules in the EGFR effective mutation group and the non-effective mutation group. Logistic regression analysis was used to explore the independent risk factors of EGFR mutation. The cut off value was determined using the receiver operating characteristic(ROC) curve. Of 232 cases 558 nodules of surgically resected MPLCs, EGFR mutation of 216 nodules was determined by direct DNA sequencing. Results: There were 58 males and 174 females with MPLCs(male︰female=1︰3). There were 117 cases of age ≥59 years old and 115 cases of age <59 years old. There were 192 non-smokers, accounting for 82.8% of all patients. There were 2-7 nodules in the patient's lungs, of which 170 patients had two nodules in the lungs, 44 patients had 3 nodules, and another patient had 7 nodules. Among them, 216 nodules were detected by EGFR gene, 136 were effective mutations, and 80 were non-effective mutations (including wild type and null mutation). EGFR effective mutation group and non-effective mutation group were statistically significant in lung adenocarcinoma patients with different gender, age, smoking history, histological type, and differentiation degree (P=0.006, 0.002, 0.002, 0.015, 0.025).Among them, the effective mutation group were 107 females, 85 cases≥ 59 years old, 117 cases with no smoking history, 68 acinar-based, 89 moderate differentiation. In the count data, 127 nodule edges were lobed, and only 9 nodule edges were smooth. Among the measurement data, the GGO CT value was approximately (-459±147) HU in the EGFR mutation group, with statistical difference (P=0.037). The GGO diameter was approximately (11±9)mm,P=0.279.Multivariate Logistic regression analysis showed that GGO diameter (OR=0.873, 95%CI: 0.780-0.997; P=0.018) and smooth margins (OR=0.183,95%CI: 0.041-0.824; P=0.027) were independent protective factors of effective mutations of EGFR. Conclusions: In MPLCs, effective EGFR mutation is more common, and associated with elder female, age≥59 years, non-smoking, GGO attenuation <-548 HU, moderately differentiated, predominant invasive papillary adenocarcinoma. Patients with MPLCs and these risk factors may be encouraged to have postoperative EGFR molecular test.