Molecular characterization of a selected cohort of patients affected by pulmonary metastases of malignant melanoma: Hints from BRAF, NRAS and EGFR evaluation

// Alessandra Ulivieri 1, 2 , Giuseppe Cardillo 3 , Liborio Manente 1 , Gregorino Paone 4 , Andrea Petricca Mancuso 5 , Leonardo Vigna 5 , Enrico Di Stasio 6 , Rita Gasbarra 1 , Salvatore Girlando 7 , Alvaro Leone 1 1 Anatomic Pathology Unit, San Camillo-Forlanini Hospitals, Rome, Italy 2 Laboratory of Biomedical research “Fondazione Niccolò Cusano per la Ricerca Medico-Scientifica” Niccolò Cusano University of Rome, Rome, Italy 3 Thoracic Surgery Unit, San Camillo-Forlanini Hospitals, Rome, Italy 4 Department of Respiratory Diseases, San Camillo-Forlanini Hospitals, Rome, Italy 5 Department of Medical Oncology, San Camillo-Forlanini Hospitals, Rome, Italy 6 Institute of Biochemistry and Clinical Biochemistry, Università Cattolica del Sacro Cuore, Rome, Italy 7 Anatomic Pathology Unit, S. Chiara Hospital, Trento, Italy Correspondence to: Alvaro Leone, e-mail: aleone@scamilloforlanini.rm.it Keywords: Pathology, melanoma, pulmonary metastases, BRAF, NRAS, EGFR Received: May 15, 2015 Accepted: June 20, 2015 Published: July 04, 2015 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. Materials and 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.