KIT mutations and CD117 overexpression are markers of better progression‐free survival in vulvar melanomas. (5th November 2017)

• Record Type: Journal Article
• Authors: Dias‐Santagata, D.; Selim, M.A.; Su, Y.; Peng, Y.; Vollmer, R.; Chłopik, A.; Tell‐Marti, G.; Paral, K.M.; Shalin, S.C.; Shea, C.R.; Puig, S.; Fernandez‐Figueras, M.T.; Biernat, W.; Ryś, J.; Marszalek, A.; Hoang, M.P.
• Is Part Of: British journal of dermatology. Volume 177:Number 5(2017)
• Page Start: 1376
• Page End: 1384
• Publication Date: 2017-11-05
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.15836
• Languages: English
• ISSNs: 0007-0963

Abstract

Summary: Background: Few studies have addressed prognostic markers and none has correlated molecular status and prognosis in vulvar melanomas. Objectives: To evaluate the clinicopathological features of 95 cases of vulvar melanoma. Methods: p53, CD117, Ki‐67, neurofibromin, brafv600e and nrasq61r immunostains, and molecular analyses by either targeted next‐generation or direct sequencing, were performed on available archival materials. Results: Molecular testing detected mutations in KIT (44%), BRAF (25%), NF1 (22%), TP53 (17%), NRAS (9%) and TERT promoter (9%). Co‐mutation of KIT and NF1 and of KIT and NRAS were identified in two and one cases, respectively. KIT mutations were significantly associated with better progression‐free survival in univariate analyses. In multivariate analyses CD117 expression was significantly associated with better progression‐free survival. Tumour thickness was significantly associated with worse progression‐free and overall survival, and perineural invasion significantly correlated with reduced melanoma‐specific survival and reduced overall survival. Cases were from multiple centres and only a subset of samples was available for molecular testing. Conclusions: KIT mutations and CD117 overexpression are markers of better progression‐free survival. In addition to its prognostic value, molecular testing may identify cases that might respond to targeted agents or immunotherapeutic approaches. Abstract : What's already known about this topic? Vulvar melanomas are rare, with poorer prognoses than conventional cutaneous melanomas. To date, few studies have addressed prognostic markers and none has correlated molecular status and prognosis in vulvar melanomas. What does this study add? This study, involving 10 clinical institutions from the U.S.A., Spain and Poland, shows that KIT mutations and CD117 overexpression are markers of better progression‐free survival for vulvar melanoma. What is the translational message? CD117 immunostaining and KIT mutational analysis can potentially serve as prognostic markers of vulvar melanoma. Targeted inhibitors may have a therapeutic role in cases harbouring actionable mutations. Respond to this article