This study indicates that urinary IL-2 at the eighth instillation of BCG may serve as a valuable prognostic factor of treatment efficacy as well as tumor recurrence after treatment.
Purpose: Recent studies have reported that centrosome hyperamplification (CH) is closely related to chromosomal instability in bladder cancer. In this study, we investigated whether CH could be used as a prognostic biomarker for patients with bladder cancer.Experimental Design: CH was evaluated by immunohistochemistry in 50 bladder cancers (pT2: 7). In addition, numerical aberrations of chromosomes 7, 9, and 17 and gain of 20q13, on which the Aurora-A gene is located, were evaluated by fluorescence in situ hybridization, and DNA ploidy was assessed. Preliminary experiments on eight bladder cancer cell lines found that six had over 5% of CH cells associated with a gain of 20q13 and overexpression of Aurora-A; therefore, CH-positive cases (CH؉) were defined as those having over 5% of cells with >3 centrosomes per cell.Results: CH؉, 20q13 gain, chromosomal instability, and DNA aneuploidy were detected in 30 (60%), 18 (36%), 22 (44%), and 19 (38%) patients, respectively. There were significant differences in tumor number, grade, recurrence, and progression between the CH؉ and CH؊ groups. The later had significantly higher recurrence-free and progression-free survivals than the former (P ؍ 0.0028 and P ؍ 0.0070, respectively, log-rank test). Multivariate analysis revealed that CH؉ was the strongest predictor for tumor recurrence in nonmuscle invasive (pTa and pT1) bladder cancer (hazard ratio, 1.882; 95% confidence interval, 1.161-3.325; P ؍ 0.0094).Conclusions: Detection of CH may provide crucial prognostic information about tumor recurrence in bladder cancer.
Matrix metalloproteinase (MMP)-1 is associated with tumor cell invasion and metastasis, and its promoter polymorphism has been shown to influence the transcriptional level. Our study explored the association between this polymorphism and renal cell carcinoma in a Japanese population. DNA was extracted from peripheral blood and normal tissue of 119 patients with conventional renal cell carcinoma (RCC) and from 210 age-and sex-matched healthy volunteers. Genotyping was carried out using direct sequencing. In the MMP-1 gene promoter polymorphism, it was demonstrated that the frequency of the 2G/2G genotype, which is associated with higher enzyme activity, was significantly higher in patients with RCC than in controls (p ؍ 0. Renal cell carcinoma (RCC) is the third leading cause of death among urologic tumors, accounting for about 2% of adult malignancies. 1 Although the rate of incidental detection of RCC has increased with the improvement of diagnostic techniques, metastatic lesions are still found at diagnosis in about 25% of RCC patients, and there are few preventive or therapeutic means against them. 2 In this context, there is obviously a need to develop a novel screening system that includes genetic diagnosis for detection of a high-risk group, making it possible to find early RCC more efficiently. Previous epidemiologic studies have shown that family history is associated with RCC, 3 but little is known about its risk factors.Matrix metalloproteinases (MMPs) are playing a crucial role in the process of tumor invasion and metastasis by degrading the extracellular matrices (ECMs) and connective tissues around tumor cells. 4 -6 Among MMP gene family members, the MMP-1 gene, located at 11q22, is widely expressed in a variety of tumor cells. 7,8 Murray et al. have demonstrated that expression of MMP-1 was associated with poor prognosis in colorectal and esophageal cancers. 9,10 Recent reports have revealed that the guanine insertion polymorphism (2G) at the nucleotide position Ϫ1607 in the MMP-1 promoter region creates a new 5Ј-GGA-3Ј sequence that is a core recognition sequence of the binding site for the Ets transcription factors, resulting in higher transcriptional activity. 11 Accumulating evidence has demonstrated the association of this polymorphism with several human malignancies including ovarian, 12 colorectal 13,14 and lung cancers 15 as well as cutaneous malignant melanoma. 16 This suggests that MMP-1 might be a common susceptibility gene to various tumors. In our study, we therefore examined whether the MMP-1 promoter polymorphism is associated with RCC.
MATERIAL AND METHODS
DNA samplesIn total, 119 patients (85 male and 34 female) with pathologically confirmed conventional RCC and 210 age-and sex-matched control individuals were enrolled in our study. The mean ages of the patient and control groups were 61.5 years (range 32-84) and 61.0 (range 34 -99), respectively.
Our results suggest that risk group stratification based on preoperative clinical T stage, voided urine cytology, and WBC counts may be useful for selection of UUT-UC patients for neoadjuvant chemotherapy. Prospective studies with larger numbers of patients and a longer follow-up period are needed to confirm our results.
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