C-kit protein expression correlated with activating mutations in KIT gene in oral mucosal melanoma
C-kit protein expression correlated with activating mutations in KIT gene in oral mucosal melanoma
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DOI：
10.1007/s00428-007-0524-2
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发表时间：
2008-01-01
期刊：
影响因子：
3.5
通讯作者：
Nagai, Noriyuki
中科院分区：
文献类型：
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作者：
Rivera, Rosario S.;Nagatsuka, Hitoshi;Nagai, Noriyuki
C-kit 是一种跨膜受体酪氨酸激酶 (RTK)，由位于 4q11-12 的原癌基因 KIT 编码。在与生殖细胞、肥大细胞和卡哈尔间质细胞相关的各种肿瘤中观察到了独立于其配体的 c-kit 激活引起的功能获得突变。 C-kit 还参与黑素细胞的发育；因此，对其与口腔粘膜黑色素瘤（OMM）肿瘤发生的关系进行了研究。使用 18 例人原发性 OMM 进行免疫组织化学和突变分析。结果显示16例c-kit蛋白阳性。非典型黑素细胞表达c-kit。所有原位成分均表达 c-kit，但只有 4 例在侵袭成分中表现出强烈表达。在四个病例中观察到错义突变，其中两个与蛋白质表达增加相关。非典型黑素细胞中的 C-kit 表达表明 c-kit 在 OMM 肿瘤发生的早期阶段的作用。 C-kit 蛋白表达与激活突变相关，表明原癌基因 KIT 在 OMM 肿瘤发生中的相关作用。
C-kit is a trans-membrane receptor tyrosine kinase (RTK) encoded by the proto-oncogene KIT located at 4q11-12. Gain-of-function mutations arising to c-kit activation independent of its ligand were observed in various tumors related to germ cells, mast cells, and interstitial cells of Cajal. C-kit also participates in melanocyte development; hence, its involvement in oral mucosal melanoma (OMM) tumorigenesis was investigated. Immunohistochemistry and mutation analysis were performed using 18 cases of human primary OMM. Results revealed 16 cases positive to c-kit protein. Atypical melanocytes expressed c-kit. All in situ components expressed c-kit, but only four cases exhibited intense expression in the invasive component. Missense mutations were observed in four cases, and two of those correlated with increased protein expression. C-kit expression in atypical melanocytes suggests the role of c-kit in the early stage of OMM tumorigenesis. C-kit protein expression correlated with activating mutations indicating the pertinent role of the proto-oncogene KIT in the tumorigenesis of OMM.