Doctorate in Health and Biological Sciences Program, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico.
Health Care Department, Oral Pathology and Medicine Master, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico.
J Oral Pathol Med. 2019 May;48(5):382-388. doi: 10.1111/jop.12849. Epub 2019 Apr 5.
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.
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.
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 and BRAF , respectively, followed by KIT (3.2%). No KIT , MITF or PTEN mutations were identified. No significant correlation was observed between mutations and immunostaining (rs = -0.057, P = 0.765).
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.
细胞增殖过度刺激的 KIT 和 MAPK 通路下游基因的突变与原发性口腔和鼻腔黑色素瘤（POSNM）有关，但目前的信息有限，无法进行个性化治疗。因此，本研究旨在确定 C-KIT 免疫组化表达与 POSNM 中 NRAS、BRAF、KIT、MITF 和 PTEN 体细胞驱动突变之间是否存在关联。
一项回顾性研究纳入了墨西哥城一家肿瘤学参考中心的 62 例肿瘤样本（17 年期间）。进行了 C-KIT 免疫组化染色。提取基因组 DNA，通过 qPCR 评估 KIT、NRAS、BRAF、MITF 和 PTEN 的热点突变。必要时应用卡方检验、Fisher 确切检验和 Mann-Whitney U 检验。显著性水平设为 P<0.05。
共纳入 62 例病例，74%的病例 C-KIT 免疫表达阳性，均表现为中/强强度。10 例（16.1%）样本至少携带一种突变，NRAS 为 6.4%，BRAF 为 6.6%，其次是 KIT（3.2%）。未发现 KIT、MITF 或 PTEN 突变。突变与免疫染色之间未观察到显著相关性（rs=-0.057，P=0.765）。
尽管 C-KIT 免疫表达较高，但 POSNM 样本中 MAPK 突变与 C-KIT 免疫组化无关联。因此，C-KIT 免疫组化不是检测 POSNM 生物治疗候选者的可靠工具。
