Prognostic significance of anaplastic lymphoma kinase rearrangement in patients with completely resected lung adenocarcinoma

Yinglei Liu, Xiangyun Ye, Yongfeng Yu, Shun Lu


Background: Reports of the prognostic significance of anaplastic lymphoma kinase (ALK) rearrangement in early stage lung adenocarcinoma have been contradictory. This study aimed to identify the associations of ALK rearrangement with clinicopathologic features and prognosis in patients with surgically resected stage I–IIIA lung adenocarcinoma.
Methods: Analysis of ALK status was performed by a fully-automated immunochemistry assay (with rabbit monoclonal Ventana D5F3 antibody) in tissue sections of 2,103 patients with surgically-resected stage I–IIIA lung adenocarcinoma. ALK positive patients were matched with negative patients in a 1:1 ratio using propensity score matching (PSM). Clinical outcomes were assessed by disease-free survival (DFS) and overall survival (OS) after surgery. Initial recurrence pattern was also investigated according to ALK status.
Results: Among 2,103 stage I–IIIA lung adenocarcinoma cases, 81 (3.9%) were ALK positive. ALK positivity was significantly associated with younger age (P<0.001), solid predominant adenocarcinoma (P<0.001), variants of invasive adenocarcinoma (P<0.001), higher frequency of pleura invasion (P=0.040), smaller tumor size (P=0.014), mediastinal lymph node involvement (N2; P<0.001) and later pathologic stage (IIIA; P=0.001). In the match cohort, ALK positivity was not associated with DFS [hazard ratio (HR), 0.58; 95% confidence interval (CI): 0.33–1.03, P=0.063] or OS (HR, 0.61; 95% CI: 0.22–1.67, P=0.334). Lymph node involvement (HR: 5.36, 95% CI, 3.01–9.65, P<0.001) and solid predominant adenocarcinoma subtype (HR, 2.02; 95% CI: 1.07–3.79; P=0.029) were the independent prognostic factors of inferior DFS, and lymph node involvement was the independent prognostic factors of worse OS (HR, 6.61; 95% CI: 2.43–17.94; P<0.001). ALK positive patients had a higher risk of developing tumor recurrence in liver (P=0.043).
Conclusions: ALK rearrangement was not an independent prognostic factor in stage I–IIIA lung adenocarcinoma patients but leaded to a higher risk of developing recurrence in liver.