ANALYSIS OF BIOLOGICAL MARKERS BENEFICIAL TO PREDICT BIOLOGIC BEHAVIOR S OF THE RENAL CELL CARCINOMAS BASED ON GENE EXPRESSION PROFILING.

【目的】肾细胞癌（RCCs）包括几种具有明显不同临床特征和生物学行为的组织病理学亚型。因此，有必要为每个病例制定策略治疗，以获得更有利的临床结果。在本研究中，我们旨在探索基于基因表达谱的rcc精确路径生物学诊断的有用生物标志物。（材料和方法）材料;从横滨市立大学医院及其附属医院进行的肾切除术标本中获得肾细胞癌组织和非肿瘤肾组织。获得患者对分子生物学分析检查的知情同意。收集的样品保存在液氮中待用。按照常规程序从材料中提取总rna，然后进行逆转录。从RCC和非肿瘤组织中分离得到的cdna分别被荧光染料染色。使用测试芯片（Test 2阵列，Affirm etrix）确认质量的cdna，使用HuGeneFL阵列（Affirm etrix）进行微阵列分析。根据荧光强度的差异，分析rcc与非肿瘤组织、不同亚型rcc之间表达差异的基因。透明细胞rcc倾向于高表达亲听因子、胰岛素样生长因子结合蛋白（IGFBP3）、血管内皮生长因子（VEGF）和缺氧诱导因子（hfs） 1α和2α。免疫组织化学证实，脂肪蛋白1优先表达。嫌色性rcc和收集管癌高表达E-cadherin（远肾素的标志物）。同时，对有和没有VHL病基因突变的RCC进行的临床病理研究显示，基因突变的RCC预后更有利。（结论）由于rcc不是一种统一的疾病实体，因此应仔细评估每种病例的生物学行为。因此，亲脂素和VHL基因突变被认为是研究rcc的重要标志。少

(OBJECT)Renal cell carcinomas (RCCs) contain several histopathological subtypes with markedly different clinical features and biological behaviors. Therefore, establishment of strategic treatments is necessary for each cases to obtain more favorable clinical outcomes. In this research, we aimed to exploration of useful biological marker for precise path biological diagnosis of RCCs based on gene expression profiling.(MATERIALS AND METHODS)1. Materials; RCC tissues and simultaneously nonneoplastic renal tissues were obtained from nephrectomy specimens performed at the Yokohama City University Hospital and the affiliated hospitals. Informed consents were obtained from the patients on examination of the molecular biological analyses. The collected samples were stored in liquid nitrogen until use.2. Total RNAs were extracted from the materials according to the routine procedures, and then reverse-transcribed. The resultant cDNAs derived from RCC and nonneoplastic tissues were separately la … More beled with fluorescent dyes. The cDNAs of which qualities were confirmed using the Test Chip (Test 2 array, Affirm etrix), were subjected to micro array analyses using HuGeneFL array (Affirm etrix).3. Based on differences of the fluorescent intensities, genes differently expressed were analyzed between RCCs and nonneoplastic tissues, and among RCCs of different subtypes.(RESULTS)1. Clear cell RCCs tended to highly express audiophile, insulin-like growth factor binding protein (IGFBP3), vascular endothelial growth factor (VEGF) and hypoxia-inducible factors(HIFs) 1αand 2α. Immunohistochemically, preferential expression Is confirmed for adipophylin.1. Chromophobe RCCs and collecting duct carcinoma showed high expression for E-cadherin, a marker for the distalnephron.2. Simultaneously preformed Clinicopathological study form RCC with and without von Hippel-Lindau (VHL) disease gene mutation revealed more favorable outcome in RCCs with gene mutation.(CONCLUSION)Because RCCs are not a uniform disease entity, biological behaviors in each case should be carefully evaluated. Based on this fact, adipophilin and VHL gene mutations were considered to be important marker to investigate RCCs. Less