Platinum-based chemoradiotherapy (CRT) as bladder conservation therapy has shown promising results for muscle-invasive bladder cancer. However, CRT might diminish survival as a result of the delay in cystectomy for some patients with non-responding bladder tumors. Because the p53 tumor suppression pathway, including its MDM2 counterpart, is important in chemotherapy-and radiotherapy-associated effects, functional polymorphisms in the TP53 and MDM2 genes could influence the response to treatment and the prognosis following CRT. We investigated associations between two such polymorphisms, and p53 overexpression, and response or survival in bladder cancer patients treated with CRT. The study group comprised 96 patients who underwent CRT for transitional cell carcinoma of the bladder. Single nucleotide polymorphisms (SNPs) in TP53 (codon 72, arginine > proline) and MDM2 (SNP309, T > G) were genotyped using PCR-RFLP, and nuclear expression levels of p53 were examined using immunohistochemistry. None of the genotypes or p53 overexpression was significantly associated with response to CRT. However, patients with MDM2 T / G + G / G genotypes had improved cancer-specific survival rates after CRT (P = 0.009). In multivariate analysis, the MDM2 T / G + G / G genotypes, and more than two of total variant alleles in TP53 and MDM2, were independently associated with improved cancer-specific survival (P = 0.031 and P = 0.015, respectively). In addition, MDM2 genotypes were significantly associated with cystectomy-free survival (P = 0.030). These results suggest that the TP53 and MDM2 genotypes might be useful prognostic factors following CRT in bladder cancer, helping patient selection for bladder conservation therapy. (Cancer Sci 2009; 100: 2376-2382 T he standard treatment for muscle-invasive urinary-bladder cancer is radical cystectomy followed by urinary diversion. However, this procedure is likely to impair the quality of life of the patient.(1) In many areas of cancer treatment, the trend in the 1990s was aimed at organ conservation using combined chemotherapy and radiation with or without conservative local surgery.(2) In invasive bladder cancer, several groups have reported the value of combined-modality therapy, including transurethral resection (TUR), radiation therapy, and platinum-based systemic chemotherapy.(1-3) With these programs, cystectomy is reserved for patients with an incomplete response or local relapse after combined-modality treatment. Five-year survival rates in the range of 50-65% have been published in these series, and approximately three-quarters of the surviving patients maintained their own bladders.(4-6) However, combined-modality therapy is not only potentially toxic but might also diminish survival as a result of the delay in cystectomy for some patients with non-responding bladder tumors.(7) It would therefore be useful to have predictors for response to the therapy and prognosis, to assist with choosing appropriate patients for bladder preservation. TP53 is a tumor suppressor gene that play...

Introduction: Few studies have examined the prognostic significance of common laboratory variables in Japanese patients with localized clear cell renal cell carcinoma (CCRCC). We evaluate the prognostic significance of preoperative laboratory variables in Japanese patients with localized CCRCC. Patients and Methods: The study included 110 Japanese patients who were pathologically confirmed as nonmetastatic CCRCC (pT1–3 N0M0) after radical nephrectomy at our institution. We assessed the clinical (including laboratory measurements) and pathological findings, with the survival rates after surgery. Results: Tumor stage and erythrocyte sedimentation rate (ESR) were identified as significant independent prognostic factors of progression-free survival in multivariate analysis. As for the prognostic factors for disease-specific survival, tumor stage and ESR had prognostic significance both in univariate and multivariate analyses. When the analysis was limited to pT1, multivariate analysis showed that only ESR was an independent prognostic factor for disease-specific survival. Conclusions: Preoperative ESR is an independent prognostic factor in Japanese patients with localized CCRCC, especially in patients with pT1.

The incidence of prostate cancer and the resultant mortality rates in Japanese men are lower compared with the rates for Caucasians; however, the Gleason score at diagnosis is higher in Japanese men compared with Caucasians. Loss of 13q is one of the most common chromosomal alterations in prostate cancer. To elucidate the difference in the rate of loss of 13q between Japanese and Caucasian men, we examined the allelic imbalance (AI) on chromosome 13q in 32 Japanese and 39 German prostate cancer patients with a fluorescent polymerase chain reaction technique using 12 microsatellite markers. Benign and malignant histology was identified by a single pathologist and laser capture microdissection was used to gather cancer cells. Although there were no statistical differences in patient background characteristics, the frequency of AI at 13q14 (D13S1253) and at 13q21 (D13S166) was significantly higher in Japanese patients compared with German patients (p = 0.0128 and p = 0.0078, respectively). The frequency of AI at 13q14 was significantly higher in tumors with high Gleason scores (GS) compared with tumors with low GS (p = 0.0478). The present observations suggest that the frequency of genetic alterations at 13q14 may underlie differences in the biological behavior of prostate cancer between Japanese and Caucasian populations.

BUBR1 may have significant potential as a biomarker for estimating disease-specific survival in patients with upper tract urothelial carcinoma treated by radical nephroureterectomy.

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