Over expression of hypoxia-inducible protein 2, hypoxia-inducible factor-1alpha and nuclear factor kappaB is putatively involved in acquired renal cyst formation and subsequent tumor transformation in patients with end stage renal failure.
OBJECTIVE
We examined hypoxia-inducible protein 2, hypoxia-inducible factor-1alpha and nuclear factor-kappaB 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.


METHODS
Immunohistochemical expression of hypoxia-inducible protein 2, hypoxia-inducible factor-1alpha and phosphorylated nuclear factor-kappaB (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.


RESULTS
Only faint or weak immunostaining for hypoxia-inducible protein 2, hypoxia-inducible factor-1alpha and phosphorylated nuclear factor-kappaB 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-1alpha. Although up-regulation of hypoxia-inducible protein 2, hypoxia-inducible factor-1alpha and phosphorylated nuclear factor-kappaB 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-1alpha and phosphorylated nuclear factor-kappaB immunostaining was prominent in clear cell renal cell carcinoma.


CONCLUSIONS
Hypoxia-inducible protein 2, hypoxia-inducible factor-1alpha and phosphorylated nuclear factor-kappaB may be involved in a continuous process of the evolution of phenotypic expression from a simple cyst to epithelial hyperplasia and eventually to tumor.
Department of Urology, Iwate Medical University School of Medicine, Morioka and Hachinohe City Hospital, Hachinohe, Japan. ryukonda@iwate-med.ac.jp
Ryuichiro
R
Konda
Jun
J
Sugimura
Fumihiko
F
Sohma
Toyomasa
T
Katagiri
Yusuke
Y
Nakamura
Tomoaki
T
Fujioka
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001707:Biopsy, Needle; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D052177:Kidney Diseases, Cystic / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics; D009392:Nephrectomy; D011336:Probability; D011379:Prognosis; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; D025521:Tumor Suppressor Proteins