Over Expression of Hypoxia-Inducible Protein 2, Hypoxia-Inducible Factor-1α and Nuclear Factor κB is Putatively Involved in Acquired Renal Cyst Formation and Subsequent Tumor Transformation in Patients With End Stage Renal Failure

PurposeWe examined hypoxia-inducible protein 2, hypoxia-inducible factor-1α and nuclear factor-κB in acquired cystic disease of the kidney associated with renal cell carcinoma to elucidate the roles of these factors in cyst formation and subsequent tumor transformation.Materials and MethodsImmunohistochemical expression of hypoxia-inducible protein 2, hypoxia-inducible factor-1α and phosphorylated nuclear factor-κB (active form) were examined in 20 normal kidney samples obtained from nephrectomy for localized renal cell carcinoma and 25 kidneys with acquired cystic disease associated renal cell carcinoma from 23 patients on dialysis.ResultsOnly faint or weak immunostaining for hypoxia-inducible protein 2, hypoxia-inducible factor-1α and phosphorylated nuclear factor-κB was observed in normal kidney tissues. In nontumor areas of the kidneys with acquired cystic disease expressions of these 3 proteins was up-regulated in tubular and cyst epithelial cells. Acquired cysts were classified into 3 types according to cyst epithelium morphology, namely flat, cuboidal and hyperplastic. Hyperplastic cysts were the predominant cysts expressing hypoxia-inducible protein 2 and hypoxia-inducible factor-1α. Although up-regulation of hypoxia-inducible protein 2, hypoxia-inducible factor-1α and phosphorylated nuclear factor-κB was observed in renal cell carcinoma, positive hypoxia-inducible protein 2 immunostaining was detected predominantly in papillary renal cell carcinoma, while positive hypoxia-inducible factor-1α and phosphorylated nuclear factor-κB immunostaining was prominent in clear cell renal cell carcinoma.ConclusionsHypoxia-inducible protein 2, hypoxia-inducible factor-1α and phosphorylated nuclear factor-κB may be involved in a continuous process of the evolution of phenotypic expression from a simple cyst to epithelial hyperplasia and eventually to tumor.