CD117 immunoexpression in oral and sinonasal mucosal melanoma does not correlate with somatic driver mutations in the MAPK pathway.

BACKGROUND: Mutations on KIT and downstream genes of MAPK pathway that overstimulate cellular proliferation have been associated with primary oral and sinonasal melanomas (POSNM), but there is limited information that allows the use of personalized therapy. Thus, the aim of the present study was to determine a possible association between the C-KIT immunohistochemical expression with the presence of somatic driver mutations in NRAS, BRAF, KIT, MITF and PTEN on POSNM. METHODS: A retrospective study included 62 tumour samples of an oncological reference centre in Mexico City (17-year period). Immunohistochemistry stain of C-KIT was carried out. Genomic DNA was obtained and used to assess hotspot mutations of KIT, NRAS, BRAF, MITF and PTEN through qPCR. Chi-square, Fisher's exact and the Mann-Whitney U tests were applied when necessary. The significance was set at P < 0.05. RESULTS: Sixty-two cases were included, 74% were positive for C-KIT immunoexpression, all exhibited moderate/strong intensity. Ten (16.1%) samples harboured at least one mutation, 6.4% and 6.6% for NRAS(Q) (61R) and BRAF(V) (600E) , respectively, followed by KIT(K624E) (3.2%). No KIT(L) (576P) , MITF or PTEN mutations were identified. No significant correlation was observed between mutations and immunostaining (rs = -0.057, P = 0.765). CONCLUSIONS: Regardless of the high immunoexpression of C-KIT, there was no association with the MAPK mutations among POSNM samples. Thus, C-KIT immunohistochemistry is not a reliable tool to detect POSNM candidates for biological therapy.