Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Take-home messageThis retrospective cohort study involved tissue microarrays of 178 bladder-tumor specimens. We found that for patients with non[en] muscle-invasive bladder cancer, hyaluronoglucosaminidase 1 (HYAL-1) expression has potential as an independent predictor of progression to muscle invasion, tumor recurrence, and metastasis.Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/ affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Mario Kramer and Judith Knapp are supported by the International Academy of Life Sciences' Biomedical Science Exchange Program fellowship. Author contributions:Vinata Lokeshwar had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Kramer, Golshani, Merseburger, Lokeshwar Acquisition of data: Kramer, Golshani, Hennelotter, Garcia Analysis and interpretation of data: Kramer, Golshani, Lokeshwar Drafting of the manuscript: Lokeshwar Critical revision of the manuscript for important intellectual content: Kuczyk, Stenzl, Soloway, Lokeshwar Objective-We evaluated whether HA and HYAL-1 can predict progression to muscle invasion and recurrence among patients with non-muscle-invasive BCa.Design, setting, and participants-Based on tissue availability, tissue microarrays were prepared from a cohort of 178 BCa specimens (144 non-muscle invasive, 34 muscle invasive). Follow-up information was available on 111 patients with non-muscle-invasive BCa (mean followup: 69.5 mo); 58 patients recurred and 25 progressed to muscle invasion (mean time to progress: 22.3 mo).Measurements-HA and HYAL-1 expression was evaluated by immunohistochemistry and graded for intensity and area of staining. Association of HA and HYAL-1 staining with BCa recurrence and muscle invasion was evaluated by univariate and multivariate models.Results and limitations-HA and HYAL-1 expression correlated with tumor grade, stage, and multifocality (p < 0.05). In non-muscle-invasive BCa specimens, HYAL-1 staining was higher (234.3 ± 52.2; 200.6 ± 61.4) if patients experienced progression to muscle invasion or recurrence when compared with no progression or recurrence (164.1 ± 48.2; 172.1 ± 57; p < 0.001). HA staining correlated with muscle ...
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