Santi Raffaella, Simi Lisa, Fucci Rossella, Paglierani Milena, Pepi Monica, Pinzani Pamela, Merelli Barbara, Santucci Marco, Botti Gerardo, Urso Carmelo, Massi Daniela
Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
Clinical Biochemistry Unit, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy.
J Clin Pathol. 2015 Feb;68(2):130-4. doi: 10.1136/jclinpath-2014-202572. Epub 2014 Nov 14.
Mucosal melanomas (MM) represent a heterogeneous tumour population that exhibits site-specific molecular profiles.
In a multicentre retrospective study, we investigated KIT aberrations in primary anorectal (AR) melanomas compared with melanoma metastatic to the gastrointestinal (GI) tract.
Primary AR MM (n=31) and GI metastatic melanoma (n=27) were studied for KIT mutations on exons 11, 13, 17 and 18 by high-resolution melting analysis, direct sequencing and c-KIT expression by immunohistochemistry. Selected cases were also investigated for increased KIT gene copy number by fluorescent in situ hybridisation.
Functional KIT mutations were demonstrated in 11/31 (35.5%) of AR melanomas and in 1/26 (3.8%) of GI melanoma metastases (p=0.004). A significant difference emerged between primary and metastatic MM with regards to KIT-positive immunostaining (p=0.002). Immunohistochemical c-KIT protein overexpression did not correlate with KIT mutational status. Increased KIT copy number was demonstrated in 5/20 AR primary cases.
The rate of functional mutations in KIT is significantly higher in AR MM than in GI metastatic melanoma. KIT protein overexpression does not correlate with KIT mutations and cannot be used for screening purposes. Recognising the molecular heterogeneity of MM helps to identify patients who require a different therapeutic approach.
黏膜黑色素瘤（MM）是一类异质性肿瘤群体，具有部位特异性分子特征。
在一项多中心回顾性研究中，我们调查了原发性肛管直肠（AR）黑色素瘤与胃肠道（GI）转移黑色素瘤中的KIT基因畸变情况。
采用高分辨率熔解分析、直接测序法研究31例原发性AR MM和27例GI转移黑色素瘤中KIT基因第11、13、17和18外显子的突变情况，并通过免疫组织化学检测c-KIT表达。部分病例还通过荧光原位杂交检测KIT基因拷贝数增加情况。
11/31（35.5%）的AR黑色素瘤和1/26（3.8%）的GI黑色素瘤转移灶中检测到功能性KIT突变（p = 0.004）。原发性和转移性MM在KIT阳性免疫染色方面存在显著差异（p = 0.002）。免疫组织化学c-KIT蛋白过表达与KIT突变状态无关。20例AR原发性病例中有5例检测到KIT拷贝数增加。
AR MM中KIT功能性突变率显著高于GI转移黑色素瘤。KIT蛋白过表达与KIT突变无关，不能用于筛查。认识到MM的分子异质性有助于识别需要不同治疗方法的患者。
