ARPP protein is selectively expressed in renal oncocytoma, but rarely in renal cell carcinomas

ARPP protein is selectively expressed in renal oncocytoma, but rarely in renal cell carcinomas
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DOI:
10.1038/modpathol.3800730
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发表时间:
2007-02-01
期刊:
影响因子:
7.5
通讯作者:
Moriyama, Masatsugu
Moriyama, Masatsugu
中科院分区:
医学1区
文献类型:
--
作者:
Shomori, Kohei;Nagashima, Yoji;Moriyama, Masatsugu

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我们最近分离出一种基因,即具有富含脯氨酸区域的锚蛋白重复蛋白(ARPP),它在骨骼肌和心肌中高度表达。我们之前的免疫组织化学分析显示,ARPP 表达在横纹肌肉瘤中增强,但在平滑肌肉瘤中几乎检测不到,这表明 ARPP 是横纹肌肉瘤的有用标记物。在本研究中,我们生成了抗 ARPP 单克隆抗体 YAS11,它与 ARPP 蛋白的 N 末端区域(氨基酸残基 1-145)发生免疫反应。此外,我们还对 100 个肾肿瘤进行了免疫组织化学分析,其中包括 14 个嗜酸细胞瘤和 86 个肾细胞癌 (RCC)。我们发现 ARPP 在 14 个嗜酸细胞瘤中的 12 个 (85.7%) 中高表达,但仅在 86 个 RCC 中的 4 个 (4.7%) 中可检测到。有趣的是,在 11 例嫌色性 RCC 中均未检测到 ARPP,这表明 ARPP 可能有助于嗜酸细胞瘤和嫌色性 RCC 的鉴别诊断。此外,我们发现ARPP在正常肾脏的部分远端肾小管中选择性表达。抗ARPP抗体免疫电镜显示,正常远端肾小管和嗜酸细胞瘤中ARPP均定位于线粒体和细胞核中,表明嗜酸细胞瘤可能源自远端肾单位,并且可能源自部分远端肾小管。
We have recently isolated a gene, Ankyrin-repeated protein with a proline-rich region (ARPP), that is highly expressed in the skeletal and cardiac muscle. Our previous immunohistochemical analysis revealed that ARPP expression was augmented in rhabdomyosarcoma but scarcely detectable in leiomyosarcoma, showing that ARPP is a useful marker for rhabdomyosarcoma. In the present study, we generated the anti-ARPP monoclonal antibody, YAS11, immunoreactive with the N-terminal region (amino-acids residues 1-145) of the ARPP protein. Further, we immunohistochemically analyzed 100 renal tumors including 14 oncocytomas, and 86 renal cell carcinomas (RCCs). We found that ARPP was highly expressed in 12 of the 14 (85.7%) oncocytomas, but was detectable in only four of the 86 (4.7%) RCCs. Interestingly, ARPP was not detected in any of 11 chromophobe RCCs, suggesting that ARPP may be useful for differential diagnosis between oncocytoma and chromophobe RCC. Furthermore, we found that ARPP was selectively expressed in part of the distal renal tubule in normal kidney. Immunoelectron microscopy with anti-ARPP antibody revealed that ARPP was localized in mitochondria and nuclei in both the normal distal renal tubule and oncocytoma, suggesting that oncocytoma may be derived from the distal nephron, and probably from part of the distal renal tubule.