ALK gene copy number gains in non-small-cell lung cancer: prognostic impact and clinico-pathological correlations

作者：Peretti U; Ferrara R; Pilotto S^*; Kinspergher S; Caccese M; Santo A; Brunelli M; Calio A; Carbognin L; Sperduti I; Garassino M; Chilosi M; Scarpa A; Tortora G; Bria E

来源：Respiratory Research, 2016, 17(1): 105.

DOI：10.1186/s12931-016-0422-8

• Lung cancer
• Anaplastic lymphoma kinase
• Copy number gain
• Prognosis
• Clinico-pathological characteristics

Background: The correlation between ALK gene copy number gain (ALK-CNG) and prognosis in the context of advanced non-small-cell lung cancer (NSCLC) remains a controversial issue. This study aimed to evaluate the association among ALK-CNG according to Fluorescent In Situ Hybridization (FISH), clinical characteristics and survival in resectable and advanced NSCLC.
Methods: Clinical and pathological data of patients with resectable and advanced NSCLC were retrospectively collected. Tumor tissues were analyzed for ALK-CNG by FISH, and patients were divided in 3 groups/patterns on the basis of ALK signals: disomic [Pattern A], 3-7 signals [Pattern B], >7 signals [Pattern C]. The association between clinical and pathological features and ALK-CNG patterns was evaluated. Disease/progression-free and overall survival (DFS/PFS and OS) were estimated using the Kaplan-Meyer method.
Results: A number of 128 (76.6 %) out of the 167 eligible patients were evaluable for ALK-CNG, displaying pattern A, B and C in 71 (42.5 %), 42 (25.1 %) and 15 (9 %) patients, respectively. Gains in ALK-CNG appear to be more frequent in smokers/former smokers than in non-smokers (74.2 % versus 20.4 %, respectively, p = 0.03). Pattern A and C seem more frequently associated with higher T-stage (T3-4), while pattern B appears more represented in lower T-stage (T 1-2) (p = 0.06). No significant differences in survival rate were observed among the above groups.
Conclusions: A high ALK-CNG pattern might be associated with smoking status and theoretically it might mirror genomic instability. The implications for prognosis should be prospectively investigated and validated in larger patients' series.

• 出版日期2016-8-25