**6. Etiology of RCC in ESRD**

Genetic profiles are distinct from classic papillary RCC or clear cell RCC. Gain of chromosomes 1, 2, 3, 6, 7, 10, 16, 17 and Y are observed in ACD-associated RCC [81, 82, 84-86]. Deletion of 3p25, +7, -Y are absent in clear cell papillary RCC [74].

The developing process of ACDK and RCC in long dialysis patients is still unclear. Several researchers reported the role of cytokine activation. Phosphorylated c-jun, the activated c-jun, which is a critical component of the AP-1 transcription factors that consist of homo- or heterodimers of basic region-leucine zipper proteins, is positive on staining of atypical hyperplastic cells in ACDK [87]. The concentration such as IL-6, -8, and VEGF is significantly high in the cystic fluid of ACDK [88]. Possibility of the relationship of calcium oxalate crystal and tumorigenesis has also been reported [17, 79, 89]. Immunohistochemical expression of oxidative stress markers, such as iNOS, 8-OHdG, and COX-2, are more frequently observed in ESRD-associated RCC than in conventional RCCs [90], since patients on dialysis are affected by oxidative stress which is caused by an imbalance between the production of reactive oxygen species and the cells ability to neutralize the reactive intermediates [91, 92].
