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. 2019 Journal of Thoracic Disease. All rights reserved.
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. 2019 Journal of Thoracic Disease. All rights reserved.
Authors: Hye Ryun Kim; Hyo Sup Shim; Jin-Haeng Chung; Young Joo Lee; Yun Kyoung Hong; Sun Young Rha; Se Hoon Kim; Sang-Jun Ha; Se Kyu Kim; Kyung Young Chung; Ross Soo; Joo Hang Kim; Byoung Chul Cho Journal: Cancer Date: 2011-06-30 Impact factor: 6.860
Authors: Adrian G Sacher; Suzanne E Dahlberg; Jennifer Heng; Stacy Mach; Pasi A Jänne; Geoffrey R Oxnard Journal: JAMA Oncol Date: 2016-03 Impact factor: 31.777
Authors: Alice T Shaw; Dong-Wan Kim; Ranee Mehra; Daniel S W Tan; Enriqueta Felip; Laura Q M Chow; D Ross Camidge; Johan Vansteenkiste; Sunil Sharma; Tommaso De Pas; Gregory J Riely; Benjamin J Solomon; Juergen Wolf; Michael Thomas; Martin Schuler; Geoffrey Liu; Armando Santoro; Yvonne Y Lau; Meredith Goldwasser; Anthony L Boral; Jeffrey A Engelman Journal: N Engl J Med Date: 2014-03-27 Impact factor: 91.245
Authors: Ultan McDermott; A John Iafrate; Nathanael S Gray; Toshi Shioda; Marie Classon; Shyamala Maheswaran; Wenjun Zhou; Hwan Geun Choi; Shannon L Smith; Lori Dowell; Lindsey E Ulkus; Georgiana Kuhlmann; Patricia Greninger; James G Christensen; Daniel A Haber; Jeffrey Settleman Journal: Cancer Res Date: 2008-05-01 Impact factor: 12.701
Authors: Fiona H Blackhall; Solange Peters; Lukas Bubendorf; Urania Dafni; Keith M Kerr; Henrik Hager; Alex Soltermann; Kenneth J O'Byrne; Christoph Dooms; Aleksandra Sejda; Javier Hernández-Losa; Antonio Marchetti; Spasenija Savic; Qiang Tan; Erik Thunnissen; Ernst-Jan M Speel; Richard Cheney; Daisuke Nonaka; Jeroen de Jong; Miguel Martorell; Igor Letovanec; Rafael Rosell; Rolf A Stahel Journal: J Clin Oncol Date: 2014-07-28 Impact factor: 44.544
Authors: Klarisa Rikova; Ailan Guo; Qingfu Zeng; Anthony Possemato; Jian Yu; Herbert Haack; Julie Nardone; Kimberly Lee; Cynthia Reeves; Yu Li; Yerong Hu; Zhiping Tan; Matthew Stokes; Laura Sullivan; Jeffrey Mitchell; Randy Wetzel; Joan Macneill; Jian Min Ren; Jin Yuan; Corey E Bakalarski; Judit Villen; Jon M Kornhauser; Bradley Smith; Daiqiang Li; Xinmin Zhou; Steven P Gygi; Ting-Lei Gu; Roberto D Polakiewicz; John Rush; Michael J Comb Journal: Cell Date: 2007-12-14 Impact factor: 41.582