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- Title
ALK gene copy number gains in non-small-cell lung cancer: prognostic impact and clinico-pathological correlations.
- Authors
Peretti, U.; Ferrara, R.; Pilotto, S.; Kinspergher, S.; Caccese, M.; Santo, A.; Brunelli, M.; Caliò, A.; Carbognin, L.; Sperduti, I.; Garassino, M.; Chilosi, M.; Scarpa, A.; Tortora, G.; Bria, E.
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.<bold>Trial Registration: </bold>We confirm that all the study was performed in accordance with relevant guidelines and regulations and that all the protocol (part of a larger project MFAG 2013 N.14282) was approved by the local Ethics Committee of the Azienda Ospedaliera Universitaria Integrata of Verona on November 11st, 2014.
- Subjects
PROTEIN genetics; LUNG cancer; PROGNOSIS; ANAPLASTIC lymphoma kinase; TUMORS; DATABASES; DISEASE susceptibility; GENES; GENETICS; LUNG tumors; GENETIC mutation; PNEUMONECTOMY; SMOKING; TIME; TRANSFERASES; PHENOTYPES; FLUORESCENCE in situ hybridization; TREATMENT effectiveness; PROPORTIONAL hazards models; RETROSPECTIVE studies; DISEASE progression; KAPLAN-Meier estimator; GENOTYPES
- Publication
Respiratory Research, 2016, Vol 17, p1
- ISSN
1465-9921
- Publication type
journal article
- DOI
10.1186/s12931-016-0422-8