ObjectivesTo investigate the association between the expression of nestin, a class VI intermediate filament protein, and pathologic features or survival in patients with urothelial carcinoma of the bladder (UCB).MethodsNestin expression in tumor cells was immunohistochemically studied in 93 patients with UCB who underwent radical cystectomy with pelvic lymphadenectomy. The associations with clinicopathologic parameters were evaluated. Kaplan–Meier survival analysis and Cox proportional hazards models were used to estimate the effect of nestin expression on survival.ResultsNestin expression in cystectomy specimens was observed in 13 of 93 patients (14.0%). Nestin expression was associated with pathologic tumor stage (p = 0.006). Nestin-negative patients had better overall survival compared with nestin-positive patients (log-rank p = 0.0148). Univariable analysis indicated that nestin expression, lymphovascular invasion, and lymph node status were significantly associated with cancer-specific survival (hazard ratios, 2.78, 2.15, and 2.80, respectively). On multivariable analysis, nestin expression and lymph node status were independent prognostic factors in cancer-specific survival (hazard ratios, 2.45 and 2.65, respectively).ConclusionsThe results suggest that nestin expression is a novel independent prognostic indicator for patients with UCB and a potentially useful marker to select patients who may be candidates for adjuvant chemotherapy.

Secreted proteins play essential roles in the process of tumorigenesis, and the analysis of tumorsecreted proteins has been suggested as a promising strategy for identifying cancer biomarkers. In this study, we performed proteomic analysis to identify proteins secreted from bladder cancer cell lines that are recognized by autoantibodies in sera from patients with bladder cancer. In addition, autoantibodies against the identified proteins were validated using a dot-blot array with sera from patients with bladder cancer and normal controls. As the results, we detected twenty-five and thirty-two immunoreactive spots in sera from patients with high-and low-grade bladder cancer, respectively. In addition, validation analysis revealed that serum IgG levels of anti-calreticulin and matrix metalloproteinase-2 (MMP2) autoantibodies were significantly higher in bladder cancer patients than in normal controls (both P < 0.05). Furthermore, the serum IgG level of anti-MMP2 autoantibody was significantly higher in patients with high-compared to low-grade bladder cancer (P < 0.05). On multivariate analysis, the serum IgG level of anti-MMP2 autoantibody was an independent predictor of cancer-specific survival (P < 0.05). Based on these findings, serum IgG levels of anti-calreticulin and MMP2 autoantibodies may be novel biomarker candidates for bladder cancer and its clinical outcome.Bladder cancer (BC) is the 7th most common cancer in men and the 17th most common in women in the world. The incidence of BC has been increasing in Japan, and it was about 20 and 5 per 100,000 Japanese males and females in 2002 (22). Approximately 75-85% of BC are diagnosed as non-muscle-invasive bladder cancer (NMIBC) at the first diagnosis, and around 70% of cases present as pTa, 20% as pT1, and 10% as carcinoma in situ lesions (23).NMIBC has a tendency to recur (50-70%) and may progress (10-20%) to a higher grade and/or muscleinvasive BC in time, which might lead to high cancer-specific mortality (46). The histological tumor grade is one of the clinical factors associated with outcomes of patients with NMIBC. High-grade NMIBC generally shows a more aggressive behavior than the low-grade form, and increases the risk of a poorer prognosis (3, 32). Due to the unfavorable prognosis associated with high-grade NMIBC, differential diagnosis between high-and low-grade NMIBC might be crucial for more appropriate follow-up and aggressive treatment. Cystoscopy and urine cytology are commonly used techniques for the diagnosis and surveillance of BC. Cystoscopy can identify most papillary and

PPP1CA is a candidate sero-diagnostic and prognostic marker for patients with BC.

malignancy, chronic indwelling catheter, and glomerular disease were excluded. The risk factors specified by the current AUA MH guidelines include smoking history, irritative voiding symptoms, chemotherapy exposure, and pelvic irradiation. Univariate and multivariate logistic regression analyses were performed to explore the association between these risk factors and the presence of genitourinary malignancy. Covariates analyzed included age, gender, number of RBC/HPF (<50 versus 50), and previous urologic history (e.g. BPH, stones).RESULTS: Among 1761 patients evaluated for first-time MH, 15 (0.85%) urologic malignancies were detected, including 7 renal cancers and 8 bladder cancers. On multivariate analysis, male gender (HR¼4.16, p¼0.04), positive smoking history (HR¼6.02, p¼0.01), and presence of irritative voiding symptoms (HR¼5.99, p¼0.01) significantly increased risk for urologic malignancy. Age >50 years was associated with malignancy on univariate, but not multivariate analysis. Chemotherapy exposure, pelvic irradiation and number of RBC on urinalysis were not predictive of malignancy.CONCLUSIONS: MH can serve as an early indicator of urologic malignancy, however, its presence may not always warrant a comprehensive work-up. Male gender, positive smoking history, and irritative voiding symptoms were identified as risk-factors independently predictive of malignancy and thus, their presence justifies a thorough evaluation. In patients without these risk factors, the universal application of CT urography should be judiciously considered.

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