Young A N, Amin M B, Moreno C S, Lim S D, Cohen C, Petros J A, Marshall F F, Neish A S
Department of Pathology, Emory University School of Medicine, Atlanta, USA.
Am J Pathol. 2001 May;158(5):1639-51. doi: 10.1016/S0002-9440(10)64120-X.
The expression patterns of 7075 genes were analyzed in four conventional (clear cell) renal cell carcinomas (RCC), one chromophobe RCC, and two oncocytomas using cDNA microarrays. Expression profiles were compared among tumors using various clustering algorithms, thereby separating the tumors into two categories consistent with corresponding histopathological diagnoses. Specifically, conventional RCCs were distinguished from chromophobe RCC/oncocytomas based on large-scale gene expression patterns. Chromophobe RCC/oncocytomas displayed similar expression profiles, including genes involved with oxidative phosphorylation and genes expressed normally by distal nephron, consistent with the mitochondrion-rich morphology of these tumors and the theory that both lesions are related histogenetically to distal nephron epithelium. Conventional RCCs underexpressed mitochondrial and distal nephron genes, and were further distinguished from chromophobe RCC/oncocytomas by overexpression of vimentin and class II major histocompatibility complex-related molecules. Novel, tumor-specific expression of four genes-vimentin, class II major histocompatibility complex-associated invariant chain (CD74), parvalbumin, and galectin-3-was confirmed in an independent tumor series by immunohistochemistry. Vimentin was a sensitive, specific marker for conventional RCCs, and parvalbumin was detected primarily in chromophobe RCC/oncocytomas. In conclusion, histopathological subtypes of renal epithelial neoplasia were characterized by distinct patterns of gene expression. Expression patterns were useful for identifying novel molecular markers with potential diagnostic utility.
利用cDNA微阵列分析了7075个基因在4例传统型（透明细胞）肾细胞癌（RCC）、1例嫌色细胞RCC和2例嗜酸细胞瘤中的表达模式。使用各种聚类算法比较肿瘤之间的表达谱，从而将肿瘤分为两类，与相应的组织病理学诊断一致。具体而言，基于大规模基因表达模式，传统型RCC与嫌色细胞RCC/嗜酸细胞瘤得以区分。嫌色细胞RCC/嗜酸细胞瘤表现出相似的表达谱，包括与氧化磷酸化相关的基因以及远端肾单位正常表达的基因，这与这些肿瘤富含线粒体的形态以及两种病变在组织发生学上均与远端肾单位上皮相关的理论相符。传统型RCC中线粒体和远端肾单位基因表达下调，并通过波形蛋白和II类主要组织相容性复合体相关分子的过表达进一步与嫌色细胞RCC/嗜酸细胞瘤区分开来。通过免疫组织化学在一个独立的肿瘤系列中证实了波形蛋白、II类主要组织相容性复合体相关恒定链（CD74）、小白蛋白和半乳糖凝集素-3这4个基因的新型肿瘤特异性表达。波形蛋白是传统型RCC的敏感、特异性标志物，小白蛋白主要在嫌色细胞RCC/嗜酸细胞瘤中检测到。总之，肾上皮肿瘤的组织病理学亚型具有独特的基因表达模式。表达模式有助于识别具有潜在诊断用途的新型分子标志物。
