KIT Mutations and CD117 Overexpression Are Markers of Better Progression-Free Survival in Vulvar Melanomas

Abstract

Background

Few studies have addressed prognostic markers and none has correlated molecular status and prognosis in vulvar melanomas.

Objectives and Methods

We evaluated the clinicopathologic features of 95 cases. 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 case, respectively. KIT mutations significantly associated with better progression-free survival in univariate analyses. In multivariate analyses CD117 expression was significantly associated with better progression-free survival. Tumor thickness was significantly associated with worse progression-free and overall survival, and perineural invasion significantly correlated with reduced melanoma-specific survival and with reduced overall survival.

Limitation

Cases were from multiple centers and only a subset of samples was available for molecular testing.

Conclusion

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.

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