C-kit expression in renal oncocytomas and chromophobe renal cell carcinomas
C-kit expression in renal oncocytomas and chromophobe renal cell carcinomas
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DOI：
10.1016/j.humpath.2005.01.011
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发表时间：
2005-03-01
期刊：
影响因子：
3.3
通讯作者：
Yang, XMJ
中科院分区：
文献类型：
--
作者：
Huo, L;Sugimura, J;Yang, XMJ
C-KIT编码膜结合的酪氨酸激酶试剂盒，它在几种类型的人类肿瘤中都有表达。最近，KIT被认为是嫌色肾细胞癌(RCC)和肾血管平滑肌脂肪瘤的标志物。然而，该分子在其他肾脏肿瘤中的表达还没有得到充分的研究，特别是在形态上类似于嫌色RCC的嗜酸细胞瘤中。在这项研究中，我们分析了17例嫌色肾癌和20例肾嗜酸细胞瘤中c-kit信使RNA(MRNA)的水平。此外，在组织芯片(TMA)上对226例肾肿瘤(包括嫌色肾癌40例、嗜酸细胞瘤41例、透明细胞肾癌40例、肾血管平滑肌脂肪瘤29例和乳头状肾癌21例)进行了KIT蛋白的全面免疫组织化学分析，并与25例嫌色肾癌和30例嗜酸细胞癌的免疫组织化学染色结果进行了比较。染色强度按3级评分系统进行半定量分级。所有嫌色RCC和嗜酸细胞瘤均有c-kit mRNA的显著过表达。与正常肾组织相比，嫌色肾细胞癌和嗜酸细胞瘤的mRNA表达水平分别增加了7.4倍和7.4倍。KIT在大多数嫌色肾细胞癌(TMAS中95%和常规切片中96%)和嗜酸细胞瘤(TMA中88%和常规切片中100%)中均有表达，但在肾血管肌脂肪瘤(17%)、乳头状RCC(5%)和透明细胞RCC(3%)中少见。此外，嫌色肾癌(1.93)和嗜酸细胞瘤(2.07)TMA的平均KIT免疫反应性强于其他类型的肾肿瘤，包括血管肌脂肪瘤(0.17)、乳头状肾癌(0.05)和透明细胞肾癌(0.03)。综上所述，我们发现c-kit基因在c-kit基因芯片中的表达显著增加，而KIT蛋白的过表达通过免疫组织化学方法不仅在嫌色肾细胞癌中显著升高，在嗜酸细胞瘤中也一样。相比之下，在评估的大多数其他类型的肾细胞肿瘤中未检测到KIT的免疫组织化学表达。C-kit在这些肾脏肿瘤中的差异表达可能具有诊断和治疗意义。(C)2005年，爱思唯尔公司出版。
C-kit encodes the membrane-bound tyrosine kinase KIT, whose expression has been identified in several types of human neoplasms. Recently, KIT has been reported to be a marker for chromophobe renal cell carcinoma (RCC) and renal angiomyolipoma. However, expression of this molecule has not been adequately studied in other renal tumors, particularly oncocytoma, which may morphologically resemble chromophobe RCC. In this study, we analyzed c-kit messenger RNA (mRNA) levels in 17 chromophobe RCCs and 20 renal oncocytomas obtained from complementary DNA (cDNA) microarrays. Furthermore, comprehensive immunohistochemical analysis of KIT protein using a monoclonal antibody was performed in 226 renal tumors including chromophobe RCC (n = 40), oncocytoma (n = 41), clear-cell RCC (n = 40), renal angiomyolipoma (n = 29), and papillary RCC (n = 21) on tissue microarrays (TMAs) and was compared with immunostaining results from 25 chromophobe RCCs and 30 oncocytomas using standard sections. The staining intensity was semiquantitatively graded on a 3-tier scoring system. All chromophobe RCCs and oncocytomas showed significant overexpression of c-kit mRNA. The average increase of mRNA compared with normal kidney tissue was 7.4-fold for chromophobe RCCs and 7.4-fold for oncocytomas. Immunohistochemical expression of KIT was found in most chromophobe RCCs (95% in TMAs and 96% in conventional sections) and oncocytomas (88% in TMAs and 100% in conventional sections) but was infrequently observed in renal angiomyolipomas (17%), papillary RCCs (5%), and clear-cell RCCs (3%). Furthermore, the average KIT immunoreactivity in TMAs was stronger in chromophobe RCC (1.93) and oncocytoma (2.07) than in other subtypes of renal tumors tested, including angiomyolipomas (0.17), papillary RCCs (0.05), and clear-cell RCCs (0.03). In conclusion, we found a significant elevation of c-kit mRNA by cDNA expression microarrays and overexpression of KIT protein by immunohistochemistry not only in chromophobe RCCs but also in oncocytomas. In contrast, immunohistochemical expression of KIT was not detected in most other types of renal cell tumors evaluated. The differential expression of c-kit in these renal tumors may have diagnostic and therapeutic implications. (c) 2005 Published by Elsevier Inc.