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202PCOEXISTENCE OF EGFR MUTATIONS WITH ALK, ROS1 OR RET REARRANGEMENTS IN LUNG ADENOCARCINOMA: A CLINICOPATHOLOGICAL ANALYSIS FROM 646 CHINESE PATIENTS WITH LUNG ADENOCARCINOMA.

ABSTRACT Aim: We investigated the incidence of concomitant EGFR mutations and ALK, ROS1 or RET rearrangements in Chinese patients with lung adenocarcinoma and analyzed the clinicopathological characteristics of concomitant EGFR mutations with known fusion genes in lung adenocarcinoma. Methods: We screened 646 patients with lung adenocarcinoma for EGFR using amplification-refractory mutation system (ARMS) assay, and for ALK, ROS1 and RET status using RT-PCR assay. All positive samples were validated by direct sequencing. The clinicopathological characteristics of dual alterations was analyzed. Results: EGFR mutations were found to coexist with fusion genes in 27 (4.2%) patients with lung adenocarcinoma. Of these, EGFR/ALK, EGFR/ROS1 and EGFR/RET co-alterations were identified in 12, 7, and 8 samples, respectively. EGFR/ALK co-alterations were found in 3.2% EGFR-mutated patients and 24% ALK-rearranged patients. EGFR/ROS1 co-alterations were found in 1.9% EGFR-mutated patients and 33.3% ROS1-rearranged patients. EGFR/RET co-alterations were found in 2.2% EGFR-mutated patients and 57.1% RET-rearranged patients. The median age of patients with co-alteration were 56 (range from 28 to 75). Nineteen of 27 (70.4%) patients with dual alterations were female. There was no statistically significant difference in age, gender, smoking status, pathological stage, and adenocarcinoma subtype (according to the 2011 IASLC/ATS/ERS International Multidisciplinary Classification of Lung Adenocarcinoma) between coexistence and non-coexistence groups. RET/EGFR co-alterations seem to be more common in lepidic predominant adenocarcinoma, and ALK/EGFR co-alterations might occur more frequently in patients with resectable lesion (I-IIIa stage), with a borderline statistical significance (p = 0.062). The median overall survival (mOS) was 74.5 months in non-coexistence group, and the mOS was not reached in coexistence group. Conclusions: EGFR mutations could coexist with ALK, ROS1 or RET rearrangements, with an incidence of 1.0-1.8% of Chinese patients with lung adenocarcinoma. Coexistence of EGFR mutations with fusion genes might be associated with lepidic predominant adenocarcinoma, which is being investigated. Patients with concomitant EGFR mutations and ALK, ROS1 or RET rearrangements might have a better prognosis. Disclosure: All authors have declared no conflicts of interest.