c-met proto-oncogene expression in benign and malignant human renal tissues
c-met proto-oncogene expression in benign and malignant human renal tissues
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DOI：
10.1016/s0022-5347(01)64301-5
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发表时间：
1997-09-01
影响因子：
6.6
通讯作者：
Lin, SH
中科院分区：
文献类型：
--
作者：
Pisters, LL;ElNaggar, AK;Lin, SH
目的：肝细胞生长因子/分散因子（HGF/SF）是一种在体内外对肾上皮细胞有丝分裂作用的强有力的促分裂剂。HGF/SF通过由c-met原癌基因编码的其受体进行信号传导。我们推测HGF/SF受体c-met表达的改变可能参与某些肾细胞癌的发病机制。我们的目的是1）评估c-met蛋白在良性和恶性肾组织中的存在和定位，2）将c-met蛋白的存在与肾癌的组织学亚型、肿瘤分期和肿瘤分级相关联。材料和方法：对41例正常和恶性肾组织中的c-met蛋白进行免疫组化分析。在所有41个样本的正常肾组织中检测到c-met免疫染色。在正常肾脏中，c-met免疫染色仅限于特定肾小管节段中上皮细胞的细胞膜和/或细胞质，包括近曲小管、Henle袢的薄肢和厚肢以及集合管。肾小球、远曲小管和间质c-met染色阴性，68%的肾细胞癌c-met染色阳性，且多见于核分级较高的癌（p < 0.034），结论：c-met受体存在于正常肾脏的特定肾小管节段中，并且经常在较高核级别的肾癌中表达，提示HGF/SF-c-met通路在肾癌进展中的作用，未来的研究应该评估HGF/SF-c-met通路在正常肾生理学和肾癌生长和进展中的生物学意义。
Purpose: Hepatocyte growth factor/scatter factor (HGF/SF) is a potent mitogen to renal epithelial cells in vitro and in vivo. HGF/SF signals through its receptor which is coded by the c-met proto-oncogene. We hypothesized that altered expression of the HGF/SF receptor, c-met, may be involved in the pathogenesis of certain renal cell carcinomas. Our objectives were to 1) assess the presence and localization of c-met protein in benign and malignant human renal tissues, and 2) correlate the presence of c-met protein with renal carcinoma histological subtype, tumor stage and tumor grade.Materials and Methods: Immunohistochemical analysis of c-met protein was performed in 41 normal and malignant human renal samples.Results: c-met Immunostaining was detected in the normal kidney tissue in all 41 samples. In the normal kidney c-met immunostaining was limited to the cell membrane and/or cytoplasm of epithelial cells in specific tubular segments, including the proximal convoluted tubule, thin and thick limbs of the loop of Henle, and the collecting duct. The glomeruli, distal convoluted tubule and stroma were consistently negative for c-met staining, c-met Immunostaining was detected in 68% of renal cell carcinomas and was more common in higher nuclear grade cancers (p < 0.034),Conclusions: The c-met receptor is present in specific tubular segments in the normal kidney and is frequently expressed in higher nuclear grade renal cancers, suggesting a role in renal carcinoma progression, Future studies should evaluate the biological significance of the HGF/SF-c-met pathway in normal renal physiology, and renal cancer growth and progression.