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 has 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 immune histochemical expression with the presence of somatic driver mutations in NRAS, BRAF, KIT, MITF, and PTEN on POSNM.

METHODS: A retrospective study that included 62 tumor samples of an oncological reference center in Mexico City (17-years 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 U-Mann-Whitney 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 harbored at least one mutation, 6.4% and 6.6% for NRASQ 61R and BRAFV 600E , respectively, followed by KITK 624E (3.2%). No KITL 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. This article is protected by copyright. All rights reserved.