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Oxidative stress and DNA hypermethylation status in renal cell carcinoma arising in patients on dialysis
Author(s) -
Hori Y,
Oda Y,
Kiyoshima K,
Yamada Y,
Nakashima Y,
Naito S,
Tsuneyoshi M
Publication year - 2007
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2176
Subject(s) - renal cell carcinoma , oxidative stress , dialysis , medicine , carcinogenesis , pathology , clear cell , dna methylation , gastroenterology , cancer , biology , gene expression , biochemistry , gene
Renal cell carcinoma (RCC) is more frequently observed in patients on dialysis than in patients with normal renal function. However, the mechanism underlying carcinogenesis in RCC patients on dialysis is still unclear. We hypothesized that oxidative stress affects patients on dialysis and generates new neoplasms, and therefore analysed the correlation between the influences of various markers of oxidative stress and carcinogenesis in those patients. We evaluated the immunohistochemical expression of oxidative stress markers, such as iNOS, 8‐OHdG, and COX‐2 in 42 cases on dialysis and 51 cases with normal renal function as a control. The methylation status of p16INK4a, p14ARF, VHL , and RASSF1A was analysed together with clinicopathological factors. Histologically, the papillary type was observed more frequently in dialysis RCC than in sporadic RCC. Immunohistochemically, overexpression of iNOS ( p < 0.0001) and COX‐2 ( p = 0.0002) was more frequently observed in dialysis RCC. Furthermore, the 8‐OHdG labelling index was significantly higher in dialysis RCC than in sporadic RCC. Hypermethylation of p16INK4a was more frequently found in dialysis RCC ( p < 0.05). However, no significant correlations between oxidative stress markers and DNA hypermethylation status were observed. The overexpression of iNOS, COX‐2, and 8‐OHdG in dialysis RCC suggests that patients on dialysis are affected by oxidative stress and that this effect plays an important role in the genesis of dialysis RCC. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.