关键词:肺腺癌,EGFR,ALK,ROS1

Abstract:

ObjectiveTo study relationship between gene status [epidermal growth factor receptor（EGFR）, anaplastic lymphoma kinase (ALK) and ROS proto-oncogene 1, receptor tyrosine kinase (ROS1)] in cases with pathological lung adenocarcinoma lesion of maximum diameter ≤1 cm.MethodsA total of 1 232 patients with lung adenocarcinoma lesion of maximum diameter ≤1 cm were enrolled in the Pathology department of Huadong Hospital from January 2013 to October 2020. For patients with multiple lesions, only the biggest lesion was selected. The gene status ofEGFR,ALKandROS1were identified and clinicopathological characteristics were retrospectively analyzed.ResultsThere were 387 males and 845 females，with a mean age of 54 years.There were 182 (14.8%) cases of adenocarcinomasin situ, 778 (63.1%) cases of minimal invasive adenocarcinomas, 249(20.2%) invasive non-mucinous adenocarcinomas, and 23 (1.9%) invasive mucinous adenocarcinomas. It revealed that 43.1% (352/817 cases) hadEGFRgene mutations, of which 46.9% (165/352 cases) were 21L858R mutations and 40.6% (143/352 cases) were 19Del mutations, and 0.9% (3/352 cases) were 18G719X/20S768I and 21L858R/20S768I double mutations. The rate ofEGFRmutation were 31.0% (40/129), 42.0% (208/495), 58.4% (104/178), and 0 (0/15) for adenocarcinomain situ, minimal invasive adenocarcinoma, invasive non-mucinous adenocarcinoma, and invasive mucinous adenocarcinoma, respectively.And 23.1% (3/13 cases) had differentEGFRmutation detected for different lesions in the same patient (In 13 cases with 2 lesions of lung adenocarcinoma successively, 2 cases were positive for 19Del mutation in the first postoperative lesion andEGFRwild-type in the second lesion: one case wasEGFRwild type in the first postoperative lesion and 21L858R mutation in the second lesion). The rate ofEGFRmutations was correlated with histological type and age, and not associated with sex or smoking.EGFRmutations was more likely to occur in the age group over 60 years and in invasive non-mucinous adenocarcinomas. It showed that 1.9% (22/1168 cases) were positive forALKrearrangements, with a positive rate of 5.2% in invasive non-mucinous adenocarcinomas and of 2.6% in patients ≤60 years. The positive rate ofALKrearrangement in adenocarcinomas with solid components (22.2%, 4/18) was significantly higher than that in invasive non-mucinous adenocarcinomas (5.2%, 12/233) and adenocarcinomas without solid components (1.1%, 12/1095). It showed that 0.8% (6/795 cases) were positive forROS1rearrangements, independent of sex, age, smoking and histological type. A total of 382 cases were tested forEGFR,ALKandROS1simultaneously, of which 40.6% (155/382) of the tumours containing one of these three mutations or rearrangements status, and no co-exist in either or all three.ConclusionsIn this single-center study, minimal invasive adenocarcinomas accounts for the majority (63.1%) of lung adenocarcinomas with a lesion size ≤1 cm. At least 40% of them have mutations or rearrangements in one of the three genes (EGFR,ALKandROS1)，and none of which were significantly associated with sex or smoking. The most common EGFR mutations are 21L858R and 19Del, which occur more frequently in invasive non-mucinous adenocarcinomas in the >60 age group, whileALKrearrangements occur more frequently in solid-component adenocarcinomas in the ≤60 age group. The incidence ofROS1rearrangements is low. The molecular change may be different in the same patien to with multiple adenocarcinomas，molecular testing foci is necessary for each lesion.

Key words:Lung adenocarcinoma,Epidermal growth factor receptor, Anaplastic lymphoma kinase,ROS proto-oncogene 1, receptor tyrosine kinase