{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:47:45Z","timestamp":1790430465753,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,9,17]],"date-time":"2014-09-17T00:00:00Z","timestamp":1410912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:sec><jats:title>Objectives\/Hypothesis<\/jats:title><jats:p>To determine the prognostic value of hypoxia\u2010associated markers carbonic anhydrase\u20109 (CA\u20109) and hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1) in advanced larynx and hypopharynx squamous cell carcinoma (SCCa) treated by organ preservation strategies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Retrospective cohort study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pretreatment CA\u20109 and HIF\u20101\u03b1 expression, clinicopathologic data, and tumor volume were analyzed in a series of 114 patients with T3\u20134 SCCa larynx or hypopharynx treated by (chemo)radiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Adverse prognostic factors for locoregional control were T4 classification (<jats:italic>P<\/jats:italic>\u2009=\u20090.008), and for disease\u2010specific survival were CA\u20109 positivity (<jats:italic>P =<\/jats:italic> 0.039), T4 classification (<jats:italic>P =<\/jats:italic> 0.001), larger tumor volume (<jats:italic>P =<\/jats:italic> 0.004), N1\u20133 classification (<jats:italic>P =<\/jats:italic> 0.002), and pretreatment hemoglobin\u2009&lt;\u200913.0 g\/dl (<jats:italic>P =<\/jats:italic> 0.014). With increasing CA\u20109 expression, there was a trend to increasing tumor recurrence (P<jats:sub>trend<\/jats:sub>\u2009=\u20090.009) and decreasing survival (P<jats:sub>trend<\/jats:sub>\u2009=\u20090.002). On multivariate analysis, independent variables were T4 classification (hazard ratio [HR] 13.54, <jats:italic>P =<\/jats:italic> 0.01) for locoregional failure, and CA\u20109 positivity (HR\u2009=\u20098.02, <jats:italic>P =<\/jats:italic> 0.042) and higher tumor volume (HR\u2009=\u20093.33, <jats:italic>P =<\/jats:italic> 0.007) for disease\u2010specific mortality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the first study to look specifically at T3 and T4 SCCa larynx and hypopharynx for a relationship between hypoxia\u2010associated marker expression and clinical outcome. Pretreatment immunohistochemical CA\u20109 expression is an adverse prognostic factor for disease\u2010specific survival, indicating that CA\u20109 expression may confer a more aggressive tumor phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>4. <jats:italic>Laryngoscope<\/jats:italic>, 125:E8\u2013E15, 2015<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.24933","type":"journal-article","created":{"date-parts":[[2014,9,17]],"date-time":"2014-09-17T09:04:32Z","timestamp":1410944672000},"source":"Crossref","is-referenced-by-count":23,"title":["Prognostic value of hypoxia\u2010associated markers in advanced larynx and hypopharynx squamous cell carcinoma"],"prefix":"10.1002","volume":"125","author":[{"given":"Jonathan M.","family":"Bernstein","sequence":"first","affiliation":[{"name":"University Department of Otolaryngology\u2013Head &amp; Neck Surgery Manchester Royal Infirmary and Manchester Academic Health Science Centre"},{"name":"Translational Radiobiology Group, Institute of Cancer Sciences, Manchester Academic Health Science Centre, University of Manchester"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy D.","family":"Andrews","sequence":"additional","affiliation":[{"name":"Department of Pathology Royal Liverpool University Hospital Liverpool United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick J.","family":"Slevin","sequence":"additional","affiliation":[{"name":"Translational Radiobiology Group, Institute of Cancer Sciences, Manchester Academic Health Science Centre, University of Manchester"},{"name":"Department of Head and Neck Clinical Oncology The Christie NHS Foundation Trust Manchester"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharine M. 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