Pingping Liu1, Cuiping Wang1, Shafei Wu1, Jie Gao1, Xuan Zeng2. 1. Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China. 2. Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China. E-mail: zengx88@aliyun.com.
Abstract
OBJECTIVE: To investigate ALK gene rearrangements in lung adenocarcinomas in correlation with clinicopathologic parameters including prognosis. METHODS: Fluorescence in situ hybridization (FISH) was used to detect ALK gene rearrangements in 53 cases of lung adenocarcinomas. Mutations in exons 18, 19, 20 and 21 of EGFR were analyzed by Scorpion amplification refractory mutation system (Scorpions ARMS). RESULTS: In a cohort of 53 lung adenocarcinomas, ALK gene rearrangements were identified in 6 tumors (11.3%), including 4 male and 2 female patients. Five were acinar predominant adenocarcinomas and one was mucinous adenocarcinoma (P=1.000). All tumors with the ALK rearrangements had the wild-type epidermal growth factor receptor (EGFR) gene (P=0.023). The median time of disease-free survival (DFS) in ALK positive patients and negative patients were 14 months (95%CI 8.0-20.0) and 31 months (95%CI 24.9-37.1), respectively and the difference was significant (Log-rank test, P=0.019). ALK gene rearrangements were significantly associated with early recurrence, but not tumor size, pathologic stages, histological differentiation and lymph node metastasis. CONCLUSIONS: ALK gene rearrangements are present at a higher frequency in lung adenocarcinomas of the Chinese patients. ALK gene rearrangements are mutually exclusive with EGFR mutations and associated with early tumor recurrence.
OBJECTIVE: To investigate ALK gene rearrangements in lung adenocarcinomas in correlation with clinicopathologic parameters including prognosis. METHODS: Fluorescence in situ hybridization (FISH) was used to detect ALK gene rearrangements in 53 cases of lung adenocarcinomas. Mutations in exons 18, 19, 20 and 21 of EGFR were analyzed by Scorpion amplification refractory mutation system (Scorpions ARMS). RESULTS: In a cohort of 53 lung adenocarcinomas, ALK gene rearrangements were identified in 6 tumors (11.3%), including 4 male and 2 female patients. Five were acinar predominant adenocarcinomas and one was mucinous adenocarcinoma (P=1.000). All tumors with the ALK rearrangements had the wild-type epidermal growth factor receptor (EGFR) gene (P=0.023). The median time of disease-free survival (DFS) in ALK positive patients and negative patients were 14 months (95%CI 8.0-20.0) and 31 months (95%CI 24.9-37.1), respectively and the difference was significant (Log-rank test, P=0.019). ALK gene rearrangements were significantly associated with early recurrence, but not tumor size, pathologic stages, histological differentiation and lymph node metastasis. CONCLUSIONS:ALK gene rearrangements are present at a higher frequency in lung adenocarcinomas of the Chinese patients. ALK gene rearrangements are mutually exclusive with EGFR mutations and associated with early tumor recurrence.