Pitz S, Moll R, Störkel S, Thoenes W
Lab Invest. 1987 Jun;56(6):642-53.
We examined the expression of the diverse cytokeratin (CK) polypeptides as well as vimentin in human renal cell carcinomas of various subtypes and in renal oncocytomas by applying both two-dimensional gel electrophoresis and immunocytochemistry by using polypeptide-specific monoclonal antibodies. The tumors were classified according to the guidelines of the World Health Organization, with some modifications based primarily on recently proposed cytomorphological criteria. All clear cell carcinomas (G I, G II; N = 20) co-expressed CKs nos. 8 and 18, and vimentin, with CK no. 19 being present in 13 of the 20 cases and exhibiting a heterogeneous distribution. Dedifferentiated carcinomas (G III; N = 8) also co-expressed CKs nos. 8 and 18 as well as vimentin, but in addition, exhibited CK no. 19 and, in many cases, CK no. 7; in 1 case, only vimentin was expressed. Both eosinophilic-granular (N = 3) and basophilic (small cell cuboidal; N = 6) carcinomas contained CKs nos. 8 and 18, and the co-expression of vimentin was a consistent feature of these tumors; CK no. 19 was found in all of these cases, while CK no. 7 was present in the majority. In chromophobe cell carcinomas (N = 8), in contrast to all of the other carcinoma types, no vimentin was detected in the tumor cells, with only CKs nos. 8, 18, and to a variable extent 7, being present. Similarly, oncocytomas (N = 8) lacked vimentin and exhibited only CKs nos. 8 and 18. Conspicuous scattered CK no. 19-positive cells were found in these two last tumor types. No CK polypeptides other than simple-epithelium-type CKs (nos. 7, 8, 18, and 19) were detected in any of the tumors studied. These results indicate that, in renal cell tumors, the expression of intermediate-filament proteins is strikingly correlated with the specific morphologic appearance. While the co-expression of CKs nos. 8 and 18 and vimentin was a surprisingly consistent feature of the most common subtypes of renal cell carcinomas, CK no. 19 exhibited remarkable heterogeneity of expression both within individual tumors and between different tumors, the expression patterns of this CK being correlated to the tumor subtypes. The consistent absence of vimentin in chromophobe cell carcinomas and oncocytomas makes it possible to define these as a separate class of renal cell tumors. This finding supports the view that chromophobe cell carcinomas represent a distinct tumor entity and points to their close phenotypic relationship to benign oncocytomas as well as to normal renal tubules.
我们通过二维凝胶电泳和免疫细胞化学方法,运用多肽特异性单克隆抗体,检测了不同亚型的人肾细胞癌及肾嗜酸细胞瘤中多种细胞角蛋白(CK)多肽以及波形蛋白的表达情况。肿瘤按照世界卫生组织的指导原则进行分类,并根据最近提出的细胞形态学标准进行了一些修改。所有透明细胞癌(G I、G II;N = 20)均共表达CK8和CK18以及波形蛋白,20例中有13例存在CK19,且分布不均一。去分化癌(G III;N = 8)同样共表达CK8和CK18以及波形蛋白,但此外还表达CK19,且在许多病例中表达CK7;1例仅表达波形蛋白。嗜酸性颗粒癌(N = 3)和嗜碱性癌(小细胞立方状;N = 6)均含有CK8和CK18,波形蛋白的共表达是这些肿瘤的一个一致特征;所有这些病例均发现有CK19,而大多数病例存在CK7。与所有其他癌类型不同,嫌色细胞癌(N = 8)的肿瘤细胞中未检测到波形蛋白,仅存在CK8、CK18,以及在不同程度上存在CK7。同样,肾嗜酸细胞瘤(N = 8)缺乏波形蛋白,仅表现出CK8和CK18。在这最后两种肿瘤类型中发现了明显散在的CK19阳性细胞。在所研究的任何肿瘤中均未检测到除简单上皮型CK(7、8、18和19号)以外的其他CK多肽。这些结果表明,在肾细胞肿瘤中,中间丝蛋白的表达与特定的形态学表现显著相关。虽然CK8和CK18以及波形蛋白的共表达是肾细胞癌最常见亚型的一个惊人一致的特征,但CK19在个体肿瘤内部和不同肿瘤之间均表现出显著的表达异质性,该CK的表达模式与肿瘤亚型相关。嫌色细胞癌和肾嗜酸细胞瘤中波形蛋白的持续缺失使得有可能将它们定义为一类单独的肾细胞肿瘤。这一发现支持了嫌色细胞癌代表一种独特肿瘤实体的观点,并指出了它们与良性肾嗜酸细胞瘤以及正常肾小管之间密切的表型关系。