title: Molecular characterization of a selected cohort of patients affected by pulmonary metastases of malignant melanoma: Hints from BRAF, NRAS and EGFR evaluation.
abstract: BACKGROUND
  Melanoma is highly curable in early stages but holds devastating consequences in advanced phases with a median survival of 6-10 months. Lungs are a common metastasis target, but despite this, limited data are available on the molecular status of pulmonary lesions.
  
  
  METHODS
  25 patients with surgically resected melanoma lung metastases were screened for BRAF, NRAS, CKIT and EGFR alterations. The results were correlated with time to lung metastasis (TLM), relapse-free survival after metastasectomy (RFS) and overall survival (OS).
  
  
  RESULTS
  BRAF or NRAS were mutated in 52% and 20% of cases while CKIT was unaffected. Chromosome 7 polysomy was detected in 47% of cases with 17.5% showing EGFR amplification and concomitant BRAF mutation. NRAS mutated patients developed LM within 5 yrs from primary melanoma with larger lesions compared with BRAF (mean diameter 3.3 ± 2.2cm vs 1.9 ± 1.1cm, p = 0.2). NRAS was also associated with a shorter median RFS and OS after metastasectomy. Moreover, Cox regression analysis revealed that NRAS mutation was the only predictive factor of shorter survival from primary melanoma (p = 0.039, OR = 5.5 (1.1-27.6)).
  
  
  CONCLUSIONS
  Molecular characterization identifies advanced melanoma subgroups with distinct prognosis and therapeutic options. The presence of NRAS mutation was associated to a worse disease evolution.
authors: Anatomic Pathology Unit, San Camillo-Forlanini Hospitals, Rome, Italy.|Laboratory of Biomedical research "Fondazione Niccolò Cusano per la Ricerca Medico-Scientifica" Niccolò Cusano University of Rome, Rome, Italy.
authors: Alessandra
authors: A
authors: Ulivieri
authors: Thoracic Surgery Unit, San Camillo-Forlanini Hospitals, Rome, Italy.
authors: Giuseppe
authors: G
authors: Cardillo
authors: Anatomic Pathology Unit, San Camillo-Forlanini Hospitals, Rome, Italy.
authors: Liborio
authors: L
authors: Manente
authors: Department of Respiratory Diseases, San Camillo-Forlanini Hospitals, Rome, Italy.
authors: Gregorino
authors: G
authors: Paone
authors: Department of Medical Oncology, San Camillo-Forlanini Hospitals, Rome, Italy.
authors: Andrea Petricca
authors: AP
authors: Mancuso
authors: Department of Medical Oncology, San Camillo-Forlanini Hospitals, Rome, Italy.
authors: Leonardo
authors: L
authors: Vigna
authors: Institute of Biochemistry and Clinical Biochemistry, Università Cattolica del Sacro Cuore, Rome, Italy.
authors: Enrico
authors: E
authors: Di Stasio
authors: Anatomic Pathology Unit, San Camillo-Forlanini Hospitals, Rome, Italy.
authors: Rita
authors: R
authors: Gasbarra
authors: Anatomic Pathology Unit, S. Chiara Hospital, Trento, Italy.
authors: Salvatore
authors: S
authors: Girlando
authors: Anatomic Pathology Unit, San Camillo-Forlanini Hospitals, Rome, Italy.
authors: Alvaro
authors: A
authors: Leone
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D005784:Gene Amplification; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D059146:Metastasectomy / Q000379:methods; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D010641:Phenotype; D011013:Pneumonectomy; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012307:Risk Factors; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
keywords: BRAF; EGFR; NRAS; Pathology; melanoma; pulmonary metastases