title: ALK gene copy number gains in non-small-cell lung cancer: prognostic impact and clinico-pathological correlations.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, P.le L.A. Scuro 10, 37124, Verona, Italy.
authors: U
authors: U
authors: Peretti
authors: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, P.le L.A. Scuro 10, 37124, Verona, Italy.
authors: R
authors: R
authors: Ferrara
authors: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, P.le L.A. Scuro 10, 37124, Verona, Italy. sara.pilotto.85@gmail.com.
authors: S
authors: S
authors: Pilotto
authors: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, P.le L.A. Scuro 10, 37124, Verona, Italy.
authors: S
authors: S
authors: Kinspergher
authors: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, P.le L.A. Scuro 10, 37124, Verona, Italy.
authors: M
authors: M
authors: Caccese
authors: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, P.le L.A. Scuro 10, 37124, Verona, Italy.
authors: A
authors: A
authors: Santo
authors: Department of Pathology and Diagnostics, University of Verona, Azienda Ospedaliera Universitaria Integrata, P.le L.A. Scuro 10, 37124, Verona, Italy.
authors: M
authors: M
authors: Brunelli
authors: Department of Pathology and Diagnostics, University of Verona, Azienda Ospedaliera Universitaria Integrata, P.le L.A. Scuro 10, 37124, Verona, Italy.
authors: A
authors: A
authors: Caliò
authors: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, P.le L.A. Scuro 10, 37124, Verona, Italy.
authors: L
authors: L
authors: Carbognin
authors: Biostatistics, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy.
authors: I
authors: I
authors: Sperduti
authors: Istituto Nazionale Tumori, Milan, Italy.
authors: M
authors: M
authors: Garassino
authors: Department of Pathology and Diagnostics, University of Verona, Azienda Ospedaliera Universitaria Integrata, P.le L.A. Scuro 10, 37124, Verona, Italy.
authors: M
authors: M
authors: Chilosi
authors: Department of Pathology and Diagnostics, University of Verona, Azienda Ospedaliera Universitaria Integrata, P.le L.A. Scuro 10, 37124, Verona, Italy.|ARC-NET Applied Research on Cancer Center, University of Verona, P.le L.A. Scuro 10, 37124, Verona, Italy.
authors: A
authors: A
authors: Scarpa
authors: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, P.le L.A. Scuro 10, 37124, Verona, Italy.
authors: G
authors: G
authors: Tortora
authors: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, P.le L.A. Scuro 10, 37124, Verona, Italy.
authors: E
authors: E
authors: Bria
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D056915:DNA Copy Number Variations; D016208:Databases, Factual; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D018628:Gene Dosage; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D042822:Genomic Instability; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011013:Pneumonectomy; D016016:Proportional Hazards Models; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000235:genetics; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: Anaplastic lymphoma kinase; Clinico-pathological characteristics; Copy number gain; Lung cancer; Prognosis