Sinonasal mucosal melanoma: Molecular profile and therapeutic implications from a series of 32 cases
Mario Turri–Zanoni MD
Department of Otorhinolaryngology, University of Brescia, Brescia, Italy
Search for more papers by this authorDaniela Medicina MS
Department of Pathology, University of Brescia, Brescia, Italy
Search for more papers by this authorDavide Lombardi MD
Department of Otorhinolaryngology, University of Brescia, Brescia, Italy
Search for more papers by this authorMarco Ungari MD
Department of Pathology, University of Brescia, Brescia, Italy
Search for more papers by this authorPiera Balzarini MS
Department of Pathology, University of Brescia, Brescia, Italy
Search for more papers by this authorCristina Rossini B.Tech
Department of Pathology, University of Brescia, Brescia, Italy
Search for more papers by this authorWilma Pellegrini B.Tech
Department of Pathology, University of Brescia, Brescia, Italy
Search for more papers by this authorPaolo Battaglia MD
Department of Otorhinolaryngology, University of Insubria, Varese, Italy
Search for more papers by this authorCarlo Capella MD
Department of Pathology, University of Insubria, Varese, Italy
Search for more papers by this authorPaolo Castelnuovo MD
Department of Otorhinolaryngology, University of Insubria, Varese, Italy
Search for more papers by this authorGabriele Palmedo MD
Dermatohistopathologische Gemeinschaftspraxis, Friedrichshafen, Germany
Search for more papers by this authorFabio Facchetti MD, PhD
Department of Pathology, University of Brescia, Brescia, Italy
Search for more papers by this authorHeinz Kutzner MD
Dermatohistopathologische Gemeinschaftspraxis, Friedrichshafen, Germany
Search for more papers by this authorPiero Nicolai MD
Department of Otorhinolaryngology, University of Brescia, Brescia, Italy
Search for more papers by this authorCorresponding Author
William Vermi MD
Department of Pathology, University of Brescia, Brescia, Italy
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri
Department of Pathology, University of Brescia, Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123, Brescia, ItalySearch for more papers by this authorMario Turri–Zanoni MD
Department of Otorhinolaryngology, University of Brescia, Brescia, Italy
Search for more papers by this authorDaniela Medicina MS
Department of Pathology, University of Brescia, Brescia, Italy
Search for more papers by this authorDavide Lombardi MD
Department of Otorhinolaryngology, University of Brescia, Brescia, Italy
Search for more papers by this authorMarco Ungari MD
Department of Pathology, University of Brescia, Brescia, Italy
Search for more papers by this authorPiera Balzarini MS
Department of Pathology, University of Brescia, Brescia, Italy
Search for more papers by this authorCristina Rossini B.Tech
Department of Pathology, University of Brescia, Brescia, Italy
Search for more papers by this authorWilma Pellegrini B.Tech
Department of Pathology, University of Brescia, Brescia, Italy
Search for more papers by this authorPaolo Battaglia MD
Department of Otorhinolaryngology, University of Insubria, Varese, Italy
Search for more papers by this authorCarlo Capella MD
Department of Pathology, University of Insubria, Varese, Italy
Search for more papers by this authorPaolo Castelnuovo MD
Department of Otorhinolaryngology, University of Insubria, Varese, Italy
Search for more papers by this authorGabriele Palmedo MD
Dermatohistopathologische Gemeinschaftspraxis, Friedrichshafen, Germany
Search for more papers by this authorFabio Facchetti MD, PhD
Department of Pathology, University of Brescia, Brescia, Italy
Search for more papers by this authorHeinz Kutzner MD
Dermatohistopathologische Gemeinschaftspraxis, Friedrichshafen, Germany
Search for more papers by this authorPiero Nicolai MD
Department of Otorhinolaryngology, University of Brescia, Brescia, Italy
Search for more papers by this authorCorresponding Author
William Vermi MD
Department of Pathology, University of Brescia, Brescia, Italy
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri
Department of Pathology, University of Brescia, Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123, Brescia, ItalySearch for more papers by this authorAbstract
Background
Primary sinonasal mucosal melanomas are aggressive tumors with a poor clinical control by current treatments, raising the urgent need of novel strategies.
Methods
By fluorescence in situ hybridization (FISH), direct sequencing, and immunohistochemistry, we investigate the spectrum of molecular abnormalities in a cohort of 32 cases of primary sinonasal mucosal melanomas.
Results
We found that all primary sinonasal mucosal melanomas lack BRAF V600E mutation; in addition, they are characterized by somatic mutations of NRAS (22%) and KIT (12.5%), together with amplification of RREB1 (100%) and loss of MYB (76%). The large majority of cases showed KIT protein expression (96.9%). Among tumor suppressor genes, primary sinonasal mucosal melanomas showed loss of PTEN (48.1%) and p16/INK4a (55.2%). All tested cases showed expression of pAkt and pErk, suggesting a combined activation of PI3K/Akt and RAS-mitogen-activated protein kinase (MAPK) pathways.
Conclusions
This molecular fingerprint strongly argues against the clinical efficacy of BRAF-inhibitors, but could candidate primary sinonasal mucosal melanomas to therapeutic strategies targeting RAS and KIT mutations or inhibiting PI3K-Akt-mTOR pathway. Head Neck, 2013
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