XPC epigenetic silence coupled with p53 alteration has a significant impact on bladder cancer outcome.

PURPOSE

Varied XPC genetics are related to bladder cancer susceptibility. We determined whether decreased XPC expression influences bladder cancer malignancy and clinical outcome.

MATERIALS AND METHODS

Changes in XPC and p53 expression were detected by immunochemistry in 108 bladder cancers, including 29 papillary neoplasms of low malignant potential, and 48 low and 31 high grade lesions, of which 47 were stage Ta-T1 and 61 were stage T2-T3. XPC mRNA and methylation were evaluated in fresh tissue by real-time reverse transcriptase and methylation specific polymerase chain reaction. The clinical value of altered XPC and p53 expression was analyzed in 66 bladder cancers, including 6 papillary neoplasms of low malignant potential, and 41 low and 19 high stage lesions, of which 26 were stage Ta-T1 and 40 were stage T2-T3, by the Kaplan-Meier method and Cox proportional hazards regression.

RESULTS

The XPC defect was associated with bladder cancer higher pathological grade, metastasis and p53 mutation. Patients with XPC(-)/p53(+) had shorter survival than those with bladder cancer without XPC(-)/p53(+) (p = 0.0127). Cox regression analysis showed that XPC expression may be a potential predictive factor for bladder cancer (p = 0.043). In bladder cancer xpc gene hypermethylation was significantly higher than in normal mucosa (p = 0.0437).

CONCLUSIONS

Lower mRNA may be the result of XPC hypermethylation in bladder cancer. Epigenetic defects in the XPC gene impact bladder cancer malignant behavior and may also predict poor outcome in some bladder cancer cases, as characterized by p53 pathway alteration.