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

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(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