{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T16:54:10Z","timestamp":1775494450662,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,5,28]],"date-time":"2019-05-28T00:00:00Z","timestamp":1559001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Because the hedgehog signalling pathway plays a major role in many types of cancer and can nowadays be targeted by specific compounds, we aimed to investigate the role of this pathway in squamous cell carcinoma of the head and neck.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Ninety\u2010eight treatment\u2010naive head and neck cancer specimens were immunohistologically stained for SMO, GLI\u20101, p53 and p16 expression and correlated with clinicopathological factors. Immunoreactivity for SMO and GLI\u20101 was found in 20 (20.4%) and 52 (53.1%) cases of tumours, respectively. SMO expression correlated with GLI\u20101 expression (\u03c1 = 0.258, <jats:italic>P<\/jats:italic> = 0.010) in univariate and multivariate analysis (<jats:italic>P<\/jats:italic> = 0.007, <jats:italic>t<\/jats:italic> = 2.81). In univariate analysis, high SMO expression was associated with shorter overall survival (HR = 0.56; 95% CI = 0.32\u20130.98; <jats:italic>P<\/jats:italic> = 0.044) and disease\u2010free survival (HR = 0.53; 95% CI = 0.30\u20130.95; <jats:italic>P<\/jats:italic> = 0.034). In multivariate cox regression analysis SMO expression showed a trend towards an independent predictor for shorter overall survival (HR = 0.57; 95% CI = 0.30\u20131.05; <jats:italic>P<\/jats:italic> = 0.072) and disease\u2010free survival (HR = 0.53; 95% CI = 0.28\u20131.02; <jats:italic>P<\/jats:italic> = 0.056). In head and neck cancer patients with low tumour p16 expression, SMO expression was an independent factor for overall survival (HR = 0.49; 95% CI = 0.24\u20130.98; <jats:italic>P<\/jats:italic> = 0.043) and disease\u2010free survival (HR = 0.45; 95% CI = 0.22\u20100.96; <jats:italic>P<\/jats:italic> = 0.037).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Although it needs to be confirmed in larger cohorts, our results suggest that targeting SMO might be a potentially therapeutic option in patients with head and neck cancer. In line, molecular pathological analyses including mutation analysis in the hedgehog pathway might point to additional therapeutic leads.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13860","type":"journal-article","created":{"date-parts":[[2019,3,12]],"date-time":"2019-03-12T16:49:28Z","timestamp":1552409368000},"page":"118-127","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Hedgehog pathway proteins SMO and GLI expression as prognostic markers in head and neck squamous cell carcinoma"],"prefix":"10.1111","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4437-4413","authenticated-orcid":false,"given":"Georg","family":"Richtig","sequence":"first","affiliation":[{"name":"Otto Loewi Research Center Pharmacology Section Medical University of Graz Graz Austria"},{"name":"Division of Oncology Medical University Graz Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alena M","family":"Aigelsreiter","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Medical University of Graz Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Asslaber","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Institute of Pathology Medical University of Graz Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Weiland","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery Medical University of Graz Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Pichler","sequence":"additional","affiliation":[{"name":"Division of Oncology Medical University Graz Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Eberhard","sequence":"additional","affiliation":[{"name":"Core Facility Computational Bioanalytics Center for Medical Research Medical University of Graz Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Sygulla","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Institute of Pathology Medical University of Graz Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Schauer","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Institute of Pathology Medical University of Graz Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9056-3063","authenticated-orcid":false,"given":"Gerald","family":"Hoefler","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Institute of Pathology Medical University of Graz Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariane","family":"Aigelsreiter","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Institute of 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