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ABSTRACT: We investigated whether centrosome amplification (CA) obtained from bladder washing cytology (BWC) specimens may be a useful prognostic biomarker for patients with non-muscle invasive bladder cancer (NMIBC). The study cohort included 78 patients with pathologically confirmed NMIBC. BWC specimens were obtained from all patients during transurethral resection of bladder tumor (TURBT), and CA was evaluated by immunofluorescence staining using a pericentrin polyclonal antibody. A positive case of CA was defined as a specimen in which >5% of cells contained ≥3 centrosomes per cell. CA was detected in 26.9% (21 of 78) of BWC specimens obtained from NMIBC patients. Disease progression was observed in 11.5% (9 of 78) of patients, with a median follow-up of 32 months. In univariate analyses, CA obtained from BWC specimens, initial or recurrent, and washing cytology were significantly associated with progression-free survival (P = 0.009, 0.02, and 0.03, respectively). Multivariate Cox model analyses revealed that CA was the most significant prognostic factor for disease progression (hazard ratio: 2.22, 95% confidence interval: 1.13-4.90, P = 0.022). These data suggest that analysis of CA using bladder washing cytological specimens may provide crucial predictive information regarding disease progression in NMIBC.
Cancer Genetics 01/2013;
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Taku Misumi,
Yoshiaki Yamamoto,
Yoshihiro Miyachika,
Satoshi Eguchi,
Yasuyo Chochi,
Motonao Nakao,
Kazuhiro Nagao,
Takahiko Hara, Shigeru Sakano,
Tomoko Furuya,
Atsunori Oga,
Shigeto Kawauchi,
Kohsuke Sasaki,
Hideyasu Matsuyama
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ABSTRACT: Recent studies have reported that lymphovascular invasion (LVI) is a predictor of patient prognosis in upper urinary tract urothelial carcinoma (UUTUC). DNA copy number aberrations (DCNAs) identified by array-based comparative genomic hybridization (aCGH) had not previously been examined in UUTUC. We therefore examined DCNAs in UUTUC and compared them with DCNAs in LVI. We applied aCGH technology using DNA chips spotted with 4,030 BAC clones to 32 UUTUC patients. Frequent copy number gains were detected on chromosomal regions 8p23.1 and 20q13.12, whereas frequent copy number losses were detected on chromosomal regions 13q21.1, 17p13.1, 6q16.3, and 17p11.2. DCNAs occurred more frequently in tumors with LVI than in those without it (P = 0.0002), and this parameter was more closely associated with LVI than with the tumor grade or pT stage. Disease-specific survival rate was higher in tumors without LVI than in those with it (P = 0.0120); however, tumor grade and stage were not significant prognostic factors of patient outcome. These data support our hypothesis that tumors with LVI have more genetic alterations in terms of total numbers of DCNAs than those without, and provide proof that aggressive adjuvant therapy should be considered for UUTUC patients with LVI.
Cancer Genetics 06/2012; 205(6):313-8.
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ABSTRACT: What's known on the subject? and What does the study add? Ras association domain family 1A (RASSF1A) is a tumour suppressor and regulates cell cycle, apoptosis and microtubule stability. This is the first study to identify associations between RASSF1A polymorphisms and clinicopathological parameters and survival in patients with clear cell renal cell carcinoma (CCRCC). RASSF1A genotyping may be useful for predicting the prognosis of the clinical course of CCRCC, and this finding might provide a better understanding of the mechanism underlying the development and progression of CCRCC. However, functional and prospective studies with a larger number of patients are needed to confirm the results.
• To compare Ras association domain family 1A (RASSF1A) genotypes or haplotypes with clinicopathological characteristics and survival rates of patients with clear cell renal cell carcinoma (CCRCC).
• The study cohort comprised 224 Japanese patients who underwent radical nephrectomy and had CCRCC confirmed by histopathological analysis. • Three common polymorphisms in the RASSF1A gene, 133Ala/Ser (G/T), -710C/T and -392C/T, were genotyped using TaqMan assays and haplotypes were analysed using appropriate software.
• Patients with CCRCC with RASSF1A -710TT genotype exhibited a significantly higher tumour stage and higher stage grouping than those with -710CC or -710CT (P = 0.005 and P = 0.032, respectively). • There was no significant association between 133Ala/Ser or -392C/T genotype and clinicopathological characteristics. • RASSF1A 133Ala-710T-392T haplotype and -710TT genotype were significantly associated with poorer recurrence-free survival rates (P = 0.038 and P = 0.007, respectively).
• This is the first study to identify associations between RASSF1A polymorphisms and clinicopathological parameters and survival in patients with CCRCC. • RASSF1A genotyping may be useful in predicting the prognosis of the clinical course of CCRCC, and this finding might provide a better understanding of the mechanism underlying the development and progression of CCRCC. • Functional and prospective studies with a larger number of patients are needed to confirm the results.
BJU International 04/2012; 110(7):1070-5. · 2.84 Impact Factor
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Tomoyuki Shimabukuro, Shigeru Sakano,
Kenji Matsuda,
Yoriaki Kamiryo,
Norio Yamamoto,
Yoshitaka Kaneda,
Takahito Nasu,
Yoshikazu Baba,
Akinobu Suga,
Mitsutaka Yamamoto,
Akihiko Aoki,
Kimio Takai,
Satoru Yoshihiro,
Motohiko Konishi,
Katsuhiko Imoto,
Hideyasu Matsuyama
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ABSTRACT: BACKGROUND: To verify the actual clinical benefit of docetaxel (DOC) therapy and to explore the prognostic factors that may predict overall survival in Japanese patients with castration-resistant prostate cancer (CRPC). METHODS: Baseline characteristics-matched CRPC patients who received conventional androgen-deprivation therapy (ADT) or ADT plus DOC were compared retrospectively. The primary endpoint was overall survival (OS) from primary therapy. Secondary endpoints were response of tumor(s), prostate-specific antigen (PSA) levels, and toxicity. RESULTS: Median OS was significantly longer in the DOC group (n = 117) than the control group (n = 118) (94.0 vs. 70.0 months, P = 0.0077) and the corresponding hazard ratio (HR) for death in DOC group was 0.566 [95% confidence interval (95%CI) 0.370-0.867; P = 0.0088]. Effective DOC groups [medium dose (50-69 mg/m(2)) and high dose (≥70 mg/m(2))] had significantly longer median OS than control even when survival times were calculated from the start of castration-resistant events (151 vs. 36 months; P = 0.0173) and the corresponding HR for death in the DOC group was 0.515 (95%CI 0.293-0.903; P = 0.0205). In multivariate analysis, statistically significant prognostic indicators were Gleason score, time to CRPC events, and receipt of DOC therapy. Response rate of both measurable lesion and PSA was not significantly different between each DOC dose group. Grade 3 or 4 adverse events associated with low- [30-49 mg/m(2)], medium-, and high-dose DOC were 21.9, 35.7, and 90.7%, respectively. No death due to DOC therapy was reported. CONCLUSION: Treatment with DOC improves OS from primary therapy compared with conventional ADT alone in Japanese patients with CRPC.
International Journal of Clinical Oncology 11/2011; · 1.41 Impact Factor
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Yoshiaki Yamamoto,
Taku Misumi,
Satoshi Eguchi,
Yasuyo Chochi,
Seiji Kitahara,
Motonao Nakao,
Kazuhiro Nagao,
Takahiko Hara, Shigeru Sakano,
Tomoko Furuya,
Atsunori Oga,
Shigeto Kawauchi,
Kohsuke Sasaki,
Hideyasu Matsuyama
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ABSTRACT: Recent studies have reported that centrosome amplification is closely related to chromosomal instability and patient prognosis in human malignancies. The purpose of this study was to elucidate the relationship between centrosome amplification and genomic alterations in urothelial carcinomas. Centrosomes were evaluated by immunohistochemistry using anti-γ-tubulin antibody. Array-based comparative genomic hybridization technology using DNA chips spotted with 4030 bacterial artificial chromosome clones was applied to 70 urothelial carcinomas to examine DNA copy number aberrations. Studying aberrations in the number of chromosomes 7, 9, and 17 using fluorescence in situ hybridization allowed the estimation of the degree of chromosomal instability. DNA copy number gains at 20p12.2, 5p15.2, 5p15.31, and 17q25.3 and losses at 17p12, 8p22, 2q37.3, 5q31.1, and 2q37.3 were more frequent in tumors with centrosome amplification than in those without it. The total numbers of DNA copy number aberrations and frequency of chromosomal instability were also larger in tumors with centrosome amplification than in those without it (P = .0263 and P < .0001, respectively). These parameters were more closely associated with centrosome amplification than with the subjectively assigned tumor grade (P = .0405 and P = .0020, respectively). Thus, these data suggest that centrosome amplification may have great potential as a biomarker for improved objective classification of urothelial carcinoma and estimation of prognosis.
Human pathology 06/2011; 42(12):1923-30. · 3.03 Impact Factor
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ABSTRACT: Bladder preservation therapy (BPT) has been attempted for patients with localized muscle-invasive bladder cancer. However, the indication for BPT has not yet been established. To identify patients who are good candidates for BPT, we evaluated our long-term experience with chemoradiation therapy (CRT) for bladder preservation.
Between 1994 and 2009, 82 patients with bladder cancer (clinical stage T2-N0M0) without concurrent upper urinary tract urothelial cancer were treated with CRT. Before CRT, the patients had a biopsy or resection of the tumor by transurethral resection (TUR). The response to CRT was evaluated by TUR, urine cytology and computed tomography.
Thirty-two cases (39.0%) had a pathological complete response (pCR) that was defined as no microscopic residual tumor in the bladder. After TUR, 69 cases (84.0%) achieved local control of the cancer, which was considered as a clinical complete response (cCR). There was no significant association between achievement of pCR and examined parameters. The long-term results of CRT were evaluated in cCR cases. The median follow-up was 42.8 months (range, 4.1-155.1). The 5-year overall survival rate was 77.7% and 5-year progression-free survival rate was 64.5%. Clinical T stage and type of tumor (primary or recurrence) were predictive factors for overall survival as well as progression-free survival. In addition, primary cT2 cases had significantly better prognosis than cT3-4 and recurrent cases in overall survival and progression-free survival (P= 0.008 and P= 0.046, respectively).
Cases with a primary cT2 tumor could be good candidates for BPT with radiation combined with cisplatin.
Japanese Journal of Clinical Oncology 05/2011; 41(7):902-7. · 1.78 Impact Factor
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Hideaki Ito,
Kazufumi Honda,
Reiko Satow,
Eri Arai,
Miki Shitashige,
Masaya Ono,
Tomohiro Sakuma, Shigeru Sakano,
Katsusuke Naito,
Hideyasu Matsuyama,
Tesshi Yamada
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ABSTRACT: Emerging molecular targeting therapeutics have been incorporated into the management of advanced renal cell carcinoma; however, their efficacy remains limited. The aim of this study was to catalog potential therapeutic target molecules for renal cell carcinoma.
We first selected genes up-regulated in clear cell renal cell carcinoma relative to surrounding normal kidney tissues in 10 patients (Study Cohort) using high-density exon arrays that detect all potential transcripts predicted in the human genome. The selected genes were subjected to independent validation in another set of 10 patients (Validation Cohort) using real-time reverse transcriptase polymerase chain reaction and functional screening using small interfering RNA in six clear cell renal cell carcinoma cell lines.
We identified 164 genes whose expression was significantly elevated in clear cell renal cell carcinoma (P< 0.0001 [Student's t-test] and at least a 3-fold change in transcription signal). We finally extracted 33 genes required for maintaining cell proliferation in at least two clear cell renal cell carcinoma cell lines. The 33 genes included 13 genes known to be associated with the development/progression of renal cell carcinoma, including CAIX and FLT-1, confirming the robustness of the current strategy.
Through a combination of genome-wide expression and functional assays, we identified a set of genes with high potential as targets for drug development. This method is rapid and comprehensive and could be applied to the discovery of diagnostic biomarkers and therapeutic targets for cancers other than clear cell renal cell carcinoma.
Japanese Journal of Clinical Oncology 05/2011; 41(7):847-53. · 1.78 Impact Factor
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Kazuhiro Nagao,
Yoshiaki Yamamoto,
Tomohiko Hara,
Hirotaka Komatsu,
Ryo Inoue,
Kenji Matsuda,
Hiroaki Matsumoto,
Takahiko Hara, Shigeru Sakano,
Yoshikazu Baba,
Hideyasu Matsuyama
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ABSTRACT: We aimed to evaluate the Epstein criteria and the eligibility criteria for active surveillance in the Prostate Cancer Research International study by using immunohistochemical staining.
We reviewed the clinicopathological data of 119 patients who underwent prostate biopsy, with prostate-specific antigen levels being ≤4 ng/ml. The data of patients with detected prostate cancer were compared with those of patients with clinically significant prostate cancer. To discriminate insignificant prostate cancer, immunohistochemical staining for Ki67, p53, bcl-2, BUBR1, PTEN and E-cadherin was performed.
Ki67, BUBR1 and E-cadherin staining showed significant correlation with the Gleason score. Ki67 and BUBR1 staining showed significant correlations with the Epstein criteria, and Ki67, BUBR1 and E-cadherin staining correlated with the Gleason score and Prostate Cancer Research International criteria. The sensitivity and specificity of Ki67 or BUBR1 staining in discriminating the prostate cancer cases classified as clinically insignificant according to the Epstein criteria were 62.5 and 84.2%, or 57.1 and 100%, respectively. The sensitivity and specificity of Ki67, BUBR1 or E-cadherin staining in discriminating prostate cancer cases classified as clinically insignificant according to the Prostate Cancer Research International criteria were 75 and 87.5%, 66.7 and 100% or 50 and 100%, respectively. The predictive accuracy of Ki67 and BUBR1 staining was equivalently high in relation to both sets of criteria (77.6 and 83.3%, respectively).
These data could provide pathological evidence to support the suitability of the Epstein and Prostate Cancer Research International criteria. Ki67 and BUBR1 may be potential markers in selecting candidates for active surveillance.
Japanese Journal of Clinical Oncology 01/2011; 41(4):555-64. · 1.78 Impact Factor
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Shigeru Sakano,
Hideyasu Matsuyama,
Kimio Takai,
Satoru Yoshihiro,
Yoriaki Kamiryo,
Satoshi Shirataki,
Yoshitaka Kaneda,
Osamu Hashimoto,
Keiji Joko,
Akinobu Suga,
Mitsutaka Yamamoto,
Shigeaki Hayashida,
Yoshikazu Baba,
Akihiko Aoki
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ABSTRACT: • To validate the European Association of Urology (EAU) guidelines on risk group stratification to predict recurrence in Japanese patients with stage Ta and T1 bladder tumours.
• A cohort of 592 Japanese patients who were treated with transurethral resection (TUR) and histopathologically diagnosed with Ta and T1 urothelial carcinoma of the bladder were enrolled in this retrospective study. • The primary endpoint of the present study was recurrence-free survival, and the median follow-up duration was 37 months in recurrence-free survivors.
• Multivariate Cox proportional hazards regression analysis showed that the Eastern Cooperative Oncology Group performance status (ECOG PS), prior recurrence rate, number of tumours and T category were independent predictors of time to recurrence (P < 0.05). According to the EAU guidelines for predicting recurrence, the vast majority of Japanese patients were classified into intermediate risk. • The intermediate-risk patients were further divided into intermediate-low-risk and intermediate-high-risk subgroups based on the European Organization for Research and Treatment of Cancer risk table, and a significant difference in the recurrence-free survival rates was found between these subgroups (P < 0.001). • It was also found that patients with high risk combined with intermediate-high risk had significantly poorer recurrence-free survival rates than those with low risk combined with intermediate-low risk (P < 0.001).
• This is the first report on the ECOG PS as a potentially useful predictor for bladder tumour recurrence. • The risk group stratification of the EAU guidelines for recurrence might not be applicable to Japanese patients with Ta and T1 bladder tumours, but the subgroup classification of intermediate risk could be appropriate.
BJU International 11/2010; 107(10):1598-604. · 2.84 Impact Factor
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Shigeru Sakano,
Yuji Hinoda,
Miwa Sasaki,
Takashi Wada,
Hiroaki Matsumoto,
Satoshi Eguchi,
Asano Shinohara,
Yoshihisa Kawai,
Tomohiko Hara,
Kazuhiro Nagao,
Takahiko Hara,
Katsusuke Naito,
Hideyasu Matsuyama
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ABSTRACT: Platinum-based chemoradiotherapy (CRT) as bladder conservation therapy has shown promising results for muscle-invasive bladder cancer. However, treatment-related toxicity remains a major consideration in therapeutic planning. Some common polymorphisms in genes involved in DNA repair (encoding enzymes that repair DNA damaged by platinum agents and ionizing radiation) are reported to result in modulation of the repair capacity. We investigated associations between functional genetic polymorphisms involved in DNA repair and acute toxicity of CRT to determine the predictive value of these polymorphisms for toxicity.
The study group comprised of 101 bladder cancer patients treated with platinum-based CRT, and seven polymorphisms in XPC (Lys939Gln, rs2228001), XPD (Lys751Gln, rs13181), XPG (Asp1104His, rs17655), XRCC1 (Arg399Gln, rs25487), XRCC3 (Thr241Met, rs861539), TP53 (Arg72Pro, rs1042522) and MDM2 (SNP309, T>G, rs2279744) were genotyped.
More than two total variant alleles in nucleotide excision repair genes, including XPC, XPD and XPG, were significantly associated with grade 3 or 4 neutropenia (adjusted odds ratio [aOR]: 6.8; 95% CI: 2.0-26; p = 0.0026). There were no significant associations between any genotypes and grade 2 or greater nausea/vomiting or diarrhea. Any grade 3 or 4 hematological toxicity was significantly associated with the Gln/Gln or Lys/Gln + Gln/Gln genotypes of XPC compared with Lys/Lys (aOR: 10; 95% CI: 2.0-65; p = 0.0070 or aOR: 6.3; 95% CI: 1.9-29; p = 0.0069; respectively).
These results suggest that nucleotide excision repair gene polymorphisms, especially in XPC, might potentially be predictive factors for acute toxicity of CRT for bladder cancer, helping individual patient selection for bladder conservation therapy. However, further studies with larger sample sizes are needed to draw final conclusions.
Pharmacogenomics 10/2010; 11(10):1377-87. · 3.97 Impact Factor
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ABSTRACT: To determine if the two common polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, affect tumour aggressiveness or prognosis of clear cell renal cell carcinoma (CCRCC) in Japanese patients.
MTHFR C677T and A1298C polymorphisms have been reported to cause decreased enzyme activity, which reduces the quantity of methyl groups available for DNA methylation and leads to mis-incorporation of uracil into DNA, resulting in single-strand DNA breaks. These effects might induce the accumulation of several genetic changes, leading to the development and progression of CCRCC. Therefore, we investigated the associations between MTHFR genotypes and haplotypes and the clinicopathological characteristics and survival rates in 240 Japanese patients with histopathologically confirmed CCRCC. MTHFR C677T and A1298C were genotyped and haplotypes were analysed using appropriate software.
The variant genotypes of MTHFR A1298C were significantly associated with some advanced characteristics of CCRCC in all patients, and these associations were stronger among men. However, among women, the variant genotypes of MTHFR C677T were associated with some advanced characteristics of CCRCC and the C677T variant genotypes or the 677T-1298A haplotype was significantly associated with decreased overall survival (P = 0.007 and P = 0.009, respectively).
To our knowledge, this is the first report on the association between MTHFR polymorphisms and CCRCC aggressiveness or prognosis. These results suggest that the MTHFR genotypes and haplotype might be useful, in a gender-specific manner, as predictive factors for the clinical course of CCRCC. Furthermore, these findings will contribute to the understanding of the mechanisms underlying CCRCC progression.
BJU International 08/2010; 106(3):424-30. · 2.84 Impact Factor
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ABSTRACT: There are few reliable markers to distinguish tumors with aggressive characteristics from others at the time of initial diagnosis in non-muscle-invasive bladder cancer. The purpose of this study was to identify a genomic marker that allows the prediction of prognosis for non-muscle-invasive bladder cancers. We screened the genome-wide copy number in 41 patients with non-muscle-invasive urothelial carcinoma of the bladder by array-based comparative genomic hybridization using arrays spotted with 4,030 bacterial artificial chromosome clones. A loss of 8p23.3 (clone 923) was correlated significantly with a higher histological grade (P = 0.0026) and advanced pathological stage (P = 0.0148). Both recurrence-free and progression-free survival rates were lower in patients with tumors without 8p23.3, compared with those with 8p23.3 (P = 0.0146 and 0.0473, respectively; log-rank test). These data suggest that the loss of 8p23.3 is a novel genomic marker allowing estimation of biological characteristics of non-muscle-invasive bladder cancer.
Cancer genetics and cytogenetics 07/2010; 200(1):16-22. · 1.54 Impact Factor
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Taku Misumi,
Yoshiaki Yamamoto,
Tomoyuki Murakami,
Yoshihisa Kawai,
Hideaki Ito,
Satoshi Eguchi,
Seiji Yano,
Kazuhiro Nagao,
Takahiko Hara, Shigeru Sakano,
Katsusuke Naito,
Kohsuke Sasaki,
Claudius Fuellhase,
Luis Arenas,
Jan Fichtner,
Hideyasu Matsuyama
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ABSTRACT: 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.
Urologia Internationalis 03/2010; 84(4):461-6. · 0.99 Impact Factor
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ABSTRACT: 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 Science 08/2009; 100(12):2376-82. · 3.33 Impact Factor
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ABSTRACT: Centrosome amplification, which may accelerate tumor progression through chromosomal instability, is frequently observed in human malignancies. The intercellular relation between the number of centrosomes and chromosomes, however, is poorly understood. Therefore, the relationship between centrosomes and chromosomal copy number in the same cells was investigated in bladder cancer. Centrosomes were evaluated by immunohistochemistry, using anti-gamma-tubulin antibody in eight bladder cancer cell lines. Fluorescence in situ hybridization with centromeric probes for chromosomes 7, 9, and 17 was then performed on the same cells stained with gamma-tubulin. The number of centrosomes was directly proportional to the number of chromosomes in cells with centrosome amplification, while a large intercellular variation in chromosomal copy number was detected in cells with normal numbers of centrosomes. Cancer cells with centrosome amplification of even centrosome numbers had significantly more even numbers of chromosomes. In cancer cells with four centrosomes, even numbers of chromosomes were detected more frequently (87.5%). These bladder cancer cell lines showed Aurora-A and p53 overexpression. These data indicate the occurrence of centrosome amplification with the possible mechanism of cytokinesis failure, resulting in a doubling of the number of centrosomes and chromosomes.
Cancer genetics and cytogenetics 06/2009; 191(1):38-42. · 1.54 Impact Factor
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ABSTRACT: Although photodynamic diagnosis is a powerful tool for the detection of flat urothelial tumors, false-positive fluorescent mucosa still requires further elucidation. Thus, we aimed to study the significance of nonmalignant fluorescent mucosa by a cytogenetic approach.
Sixty specimens of bladder mucosa were collected from 20 patients who were suspected of having carcinoma in situ by fluorescence cystoscopy with 5-aminolevulinic acid. To detect the copy number aberrations, the multi-color fluorescence in situ hybridization technique was performed, and the variant fractions (total fractions other than those of the modal copy number) of chromosomes 7, 9 and 17 and the chromosomal instability were determined. To delineate the relevant gene to the fluorescent mucosa, a comparative genomic hybridization technique was applied for 8 established bladder cancer cell lines, and these results were compared with the in vitro fluorescent expression experiment.
Fluorescent mucosa was detected in 33 of the 34 malignant tissue specimens (16 carcinoma in situ, 18 other transitional cell carcinomas) and in 11 of the 26 nonmalignant tissue specimens (6 dysplasia, 20 normal mucosa), with a false-positive rate of 42.3%. The variant fraction of chromosome 9 was significantly higher in fluorescent than in non-fluorescent mucosa, not only for all tissues (33 vs. 17%; p = 0.0069), but also for nonmalignant tissues (28 vs. 15%; p = 0.0225). There was no alteration in chromosome 9 in 1 cell line without fluorescent mucosa, while 5 of the 7 cell lines with fluorescent mucosa had a common deleted region on 9q24.1.
These data suggest that a substantial portion of nonmalignant fluorescent mucosa harbors alterations in chromosome 9.
Oncology 02/2009; 76(2):118-25. · 2.27 Impact Factor
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ABSTRACT: To determine candidates for bladder biopsies among Japanese primary non-muscle-invasive bladder cancer patients according to the risk of concomitant carcinoma in situ (CIS).
Between January 1992 and August 2006, 173 primary non-muscle-invasive bladder cancer cases underwent transurethral resection of the bladder tumor with bladder biopsies for the detection of CIS. Correlations between biopsy results and preoperative/pathological features were retrospectively analyzed.
Positive cytology was statistically associated with the presence of concomitant CIS in multivariate analysis (P < 0.01). Abnormal cystoscopic appearance outside the tumor almost achieved statistical significance in multivariate analysis among preoperative factors (P = 0.06). In our series, one (12.5%) of eight low-risk, 18 (24.7%) of 73 intermediate-risk and 41 (59.4%) of 69 high-risk cases had CIS in normal-looking sites, respectively. In cases with a single papillary tumor and negative cytology, one of 16 (6.3%) had concomitant CIS in their biopsy specimens at the normal-looking sites.
All non-muscle-invasive bladder cancer patients with positive cytology are candidates for additional random biopsies. Targeted biopsies should be performed for all suspicious areas in the bladder mucosa. Random biopsies should be considered in cases with the macroscopic types of cancer for predicting intermediate- and high-risk cancer.
International Journal of Urology 01/2009; 16(3):293-8. · 1.75 Impact Factor
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ABSTRACT: 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.
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.
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.
Preoperative ESR is an independent prognostic factor in Japanese patients with localized CCRCC, especially in patients with pT1.
Urologia Internationalis 01/2009; 83(3):306-10. · 0.99 Impact Factor
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ABSTRACT: To evaluate discrepancies in the detection of Bacille Calmette-Guerin (BCG)-resistant bladder cancer by cystoscopy, bladder biopsy and urinary cytology.
Between January 1992 and August 2006, 127 bladder cancer patients underwent a cycle of eight weekly BCG instillations. Four weeks after the last BCG instillation, urinary cytological analysis and cystoscopy with targeted biopsy in addition to eight-nine selected-site biopsies were performed.
Biopsy-proven cancer was found in 11/27 (40.7%), 5/42 (11.9%), and 11/58 (19.0%) of positive, suspicious, and negative cytology cases, respectively. Abnormal and normal cystoscopic findings correlated with a biopsy-proven cancer in 13/53 (24.5%) and 14/74 (18.9%) cases, respectively. The combination of a macroscopic cystoscopic suspicion and a positive cytology missed malignant cases in 15.9% of the cases. In 100 cases without biopsy-proven cancer, the rates of denuded urothelium at biopsy in the cases with positive and non-positive cytology were 7/16 (43.8%) and 16/84 (19.0%), respectively.
According to our study, routine biopsy is recommended in the evaluation of BCG treatment, even if the timing, limitations and disadvantages of the procedure should be taken into account.
International Journal of Urology 12/2008; 16(2):192-5. · 1.75 Impact Factor
