Clinicopathologic characteristics of ALK rearrangements in primary lung adenocarcinoma with identified EGFR and KRAS status.

Purpose: EGFR and KRAS genes and ALK arrangements are three genetic drivers of lung adenocarcinoma. The aim of this study was to investigate the clinicopathologic characteristics of the ALK rearrangements in patients with primary lung adenocarcinoma and with identified EGFR or KRAS status.

Methods: Patients with primary lung adenocarcinoma who had enough tissue for study were enrolled. EGFR and KRAS status were identified by DNA sequencing. ALK rearrangements were detected in a tissue microarray by using fluorescent in situ hybridization.

Results: Of 332 patients with primary lung adenocarcinoma, the frequency of the EGFR or the KRAS mutations, and the ALK rearrangements were 44.9% (149/332), 7.2% (24/332), and 9.6% (32/332), respectively. Only one (1/332, 0.3%) patient had the coexistence of the EGFR mutation (L858R at exon 21) and the ALK rearrangement. Compared with ALK-negative patients, ALK-positive patients were significantly younger (P < 0.001). The incidence of the ALK rearrangements was much higher in EGFR wild-type patients than in those with EGFR mutations (P < 0.001). There was no difference in the gender, smoking, disease stage, or histologic subtypes between the ALK-positive patients and the ALK-negative patients.

Conclusions: The ALK rearrangements are independently associated with younger age and the EGFR wild type. The EGFR mutations and the ALK rearrangements are rarely coexistent. The ALK rearrangements and the KRAS mutations are mutually exclusive.