Clinical Research Papers:

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

Alessandra Ulivieri _, Giuseppe Cardillo, Liborio Manente, Gregorino Paone, Andrea Petricca Mancuso, Leonardo Vigna, Enrico Di Stasio, Rita Gasbarra, Salvatore Girlando and Alvaro Leone

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Oncotarget. 2015; 6:19868-19879. https://doi.org/10.18632/oncotarget.4503

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Alessandra Ulivieri1,2, Giuseppe Cardillo3, Liborio Manente1, Gregorino Paone4, Andrea Petricca Mancuso5, Leonardo Vigna5, Enrico Di Stasio6, Rita Gasbarra1, Salvatore Girlando7, Alvaro Leone1

1Anatomic Pathology Unit, San Camillo-Forlanini Hospitals, Rome, Italy

2Laboratory of Biomedical research “Fondazione Niccolò Cusano per la Ricerca Medico-Scientifica” Niccolò Cusano University of Rome, Rome, Italy

3Thoracic Surgery Unit, San Camillo-Forlanini Hospitals, Rome, Italy

4Department of Respiratory Diseases, San Camillo-Forlanini Hospitals, Rome, Italy

5Department of Medical Oncology, San Camillo-Forlanini Hospitals, Rome, Italy

6Institute of Biochemistry and Clinical Biochemistry, Università Cattolica del Sacro Cuore, Rome, Italy

7Anatomic Pathology Unit, S. Chiara Hospital, Trento, Italy

Correspondence to:

Alvaro Leone, e-mail: [email protected]

Keywords: Pathology, melanoma, pulmonary metastases, BRAF, NRAS, EGFR

Received: May 15, 2015     Accepted: June 20, 2015     Published: July 04, 2015


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.

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