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

Abstract

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 NRASQ61R and BRAFV600E, respectively, followed by KITK624E (3.2%). No KITL576P, 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.

Sinonasal Mucosal Melanoma: An Update and Review of the Literature

“…Genetic profiling has identified a number of recurrent gene mutations including but not limited to NRAS, BRAF, KIT, and TERT. [42][43][44][45][46][47][48] Oncogene mutations have been identified in 41% of SNMM with insignificant difference in mutation rates between tumors located in the paranasal sinuses and the nasal cavity (30% vs. 13%, respectively, P = 0.09). 47 Chromosome gains have been found by comparative genomic hybridization in most of the cases; chromosome 1q gain in all SNMM and gains of 6p and 8q in 93% and 57%, respectively.…”

“…42 In addition, KIT mutations are found in 4%–13% of SNMM, less commonly than the 40% reported for in other sites of primary mucosal melanoma. 1,43–47,50 It is well established that IHC detection of c-KIT does not correlate with the presence or absence of c-KIT mutation in oral and SNMMs. 43…”

“…1,43–47,50 It is well established that IHC detection of c-KIT does not correlate with the presence or absence of c-KIT mutation in oral and SNMMs. 43…”

“…49 NRAS mutation is present in up to 30% of SNMM, whereas activating mutations of BRAF are infrequent in SNMM (0%-12%). 1,[43][44][45][46][47]50 Some have shown a correlation of NRAS mutation with prognosis in SNMM. 42 In addition, KIT mutations are found in 4%-13% of SNMM, less commonly than the 40% reported for in other sites of primary mucosal melanoma.…”

“…42 In addition, KIT mutations are found in 4%-13% of SNMM, less commonly than the 40% reported for in other sites of primary mucosal melanoma. 1,[43][44][45][46][47]50 It is well established that IHC detection of c-KIT does not correlate with the presence or absence of c-KIT mutation in oral and SNMMs. 43 Although higher in cutaneous melanoma, the incidence of TERT promoter mutations is lower in SNMM (8%), and its clinical significance is not well described.…”