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      Ubiquilin2 as a novel marker for detection of urothelial carcinoma cells in urine : UBIQUILIN2 IN URINE CYTOLOGY

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          Abstract

          Ubiquilin 2 (UBQLN2), an ubiquitin-related protein, is strongly expressed in urothelial carcinoma cells, in contrast to no or less expression in non-neoplastic cells; it protects cancer cells from reactive oxygen species (ROS)-induced cytotoxicity. In this study, we investigated whether UBQLN2 immunostaining, using liquid-based cytology sample could improve the accuracy of cytological urine diagnosis.

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          EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder.

          Marko Babjuk, Willem Oosterlinck, Richard Sylvester … (2008)
          To present the updated version of 2008 European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer. A systematic review of the recent literature on the diagnosis and treatment of non-muscle-invasive bladder cancer was performed. The guidelines were updated and the level of evidence and grade of recommendation were assigned. The diagnosis of bladder cancer depends on cystoscopy and histologic evaluation of the resected tissue. A complete and correct transurethral resection (TUR) is essential for the prognosis of the patient. When the initial resection is incomplete or when a high-grade or T1 tumour is detected, a second TUR within 2-6 wk should be performed. The short- and long-term risks of both recurrence and progression may be estimated for individual patients using the scoring system and risk tables. The stratification of patients to low, intermediate, and high-risk groups-separately for recurrence and progression-represents the cornerstone for indication of adjuvant treatment. In patients at low risk of tumour recurrence and progression, one immediate instillation of chemotherapy is strongly recommended. In those at an intermediate or high risk of recurrence and an intermediate risk of progression, one immediate instillation of chemotherapy should be followed by further instillations of chemotherapy or a minimum of 1 yr of bacillus Calmette-Guerin (BCG). In patients at high risk of tumour progression, after an immediate instillation of chemotherapy, intravesical BCG for at least 1 yr is indicated. Immediate cystectomy may be offered to the highest risk patients and in patients with BCG failure. The long version of the guidelines is available on www.uroweb.org. These EAU guidelines present the updated information about the diagnosis and treatment of non-muscle-invasive bladder cancer and offer the recent findings for the routine clinical application.
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            A novel human AlkB homologue, ALKBH8, contributes to human bladder cancer progression.

            Keiji Shimada, Mitsutoshi Nakamura, Satoshi Anai … (2009)
            We recently identified a novel human AlkB homologue, ALKBH8, which is expressed in various types of human cancers including human urothelial carcinomas. In examining the role and function of ALKBH8 in human bladder cancer development in vitro, we found that silencing of ALKBH8 through small interfering RNA transfection reduced reactive oxygen species (ROS) production via down-regulation of NAD(P)H oxidase-1 (NOX-1) and induced apoptosis through subsequent activation of c-jun NH(2)-terminal kinase (JNK) and p38. However, we also found that JNK and p38 activation resulted in phosphorylation of H2AX (gammaH2AX), a variant of mammalian histone H2A, which contributes to the apoptosis induced by silencing ALKBH8 and NOX-1. Silencing of ALKBH8 significantly suppressed invasion, angiogenesis, and growth of bladder cancers in vivo as assessed both in the chorioallantoic membrane assay and in an orthotopic mouse model using green fluorescent protein-labeled KU7 human urothelial carcinoma cells. Immunohistochemical examination showed high expression of ALKBH8 and NOX-1 proteins in high-grade, superficially and deeply invasive carcinomas (pT(1) and >pT(2)) as well as in carcinoma in situ, but not in low-grade and noninvasive phenotypes (pT(a)). These findings indicate an essential role for ALKBH8 in urothelial carcinoma cell survival mediated by NOX-1-dependent ROS signals, further suggesting new therapeutic strategies in human bladder cancer by inducing JNK/p38/gammaH2AX-mediated cell death by silencing of ALKBH8.
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              Surveillance for recurrent bladder cancer using a point-of-care proteomic assay.

              Jennifer H. Grossman, Chao-Yu Shen, Edward M. Messing … (2006)
              At least 50% of patients with a history of bladder cancer have recurrences, so rigorous surveillance is necessary. Cystoscopy is standard but can fail to detect some bladder cancers, so a urine test is frequently part of the evaluation. To investigate whether a point-of-care proteomic test that measures the nuclear matrix protein NMP22 in voided urine could improve detection of recurrence during monitoring of patients with a history of bladder cancer. From September 2001 to February 2002, 23 academic, private practice, and hospital facilities in 9 US states prospectively enrolled 668 consecutive patients with a history of bladder cancer in this cross-sectional study. Patients provided a voided urine sample for analysis of NMP22 protein and cytology prior to cystoscopy. Diagnosis of bladder cancer recurrence, based on cystoscopy with biopsy, was accepted as the reference standard. The performance of the NMP22 test was compared with voided urine cytology as an aid to detection. Testing for the NMP22 tumor marker was conducted in a blinded manner. Bladder cancer was diagnosed in 103 patients. Cystoscopy alone identified 91.3% of the cancers (94/103; 95% confidence interval [CI], 84.1%-95.9%). The combination of cystoscopy with the NMP22 assay detected 99.0% of the malignancies (102/103; 95% CI, 94.7%-100%; P = .005). The NMP22 assay detected 8 of 9 cancers that were not visualized during initial cystoscopy, including 7 that were high-grade. The sensitivity and specificity of the NMP22 test alone were 49.5% (51/103; 95% CI, 39.5%-59.5%) and 87.3% (493/565; 95% CI, 84.2%-89.9%), respectively. Voided cytology detected only 3 of the malignancies missed during initial cystoscopy and did not significantly increase the sensitivity of cystoscopy (94.2%; 95% CI, 87.7%-97.8%; P = .08). The noninvasive point-of-care assay for elevated urinary NMP22 protein can increase the ability to detect recurrent bladder cancer, with test results available during the patient visit.
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                Author and article information

                Journal
                Title: Diagnostic Cytopathology
                Abbreviated Title: Diagn. Cytopathol.
                Publisher: Wiley
                ISSN: 87551039
                Publication date Created: January 2016
                Publication date (Print): January 2016
                Publication date (Electronic): August 25 2015
                Volume: 44
                Issue: 1
                Pages: 3-9
                Affiliations
                [1 ]Department of Pathology; Nara Medical University School of Medicine; 840 Shijo-Cho Kashihara City Nara 634-8521 Japan
                [2 ]Department of Urology; Nara Medical University School of Medicine; 840 Shijo-Cho Kashihara City Nara 634-8521 Japan
                Article
                DOI: 10.1002/dc.23332
                PubMed ID: 26303000
                SO-VID: 89a7d98f-fca0-4ea9-a462-7d456a1fca17
                Copyright © © 2015
                License:

                http://doi.wiley.com/10.1002/tdm_license_1.1

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