{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T06:55:21Z","timestamp":1782888921067,"version":"3.54.5"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,5,4]],"date-time":"2004-05-04T00:00:00Z","timestamp":1083628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2004,9,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The tumor site is a strong clinical factor in head and neck squamous cell carcinoma (HNSCC). To clarify the biologic and clinical role of p53 alterations in HNSCC, we have examined the prevalence and the nature of p53 alterations in a large cohort of tumors from the different sites. For immunohistochemical analysis of p53 protein expression, we introduced tyramide signal amplification immunohistochemistry (TSA\u2010IHC) on a tissue microarray. This allowed the discrimination between normal low\u2010level expression and reduced or lost expression. Two hundred fifty\u2010three tumors were subjected to mutational analysis by genomic DNA sequencing, employing also the p53 <jats:italic>GeneChip<\/jats:italic> from Affymetrix. The prevalence of all p53 alterations, <jats:italic>i.e.<\/jats:italic>, mutations, overexpression and loss of expression, was significantly higher in hypopharyngeal tumors than in the other sites (<jats:italic>p<\/jats:italic> = 0.001). Laryngeal tumors showed the lowest rate of p53 alterations, but revealed a distinct mutation spectrum: most mutations affected exon 5 (<jats:italic>p<\/jats:italic> = 0.013) and the S2\u2032 domain (<jats:italic>p<\/jats:italic> = 0.002), and most hot\u2010spot 248 mutations occurred in the larynx (<jats:italic>p<\/jats:italic> &lt; 0.001). Sequencing by <jats:italic>p53<\/jats:italic><jats:italic>GeneChip<\/jats:italic> technology was shown to be only insignificantly more sensitive than dideoxy sequencing. In agreement with <jats:italic>p53<\/jats:italic> mutations occurring prior to invasiveness, their prevalence did not increase with tumor stage, and all mutation classes lacked prognostic significance. The large patient cohort of this study showed that <jats:italic>p53<\/jats:italic> is differentially affected in the different tumor sites of the head and neck, but its mode of inactivation does not play a major role in tumor progression. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.11698","type":"journal-article","created":{"date-parts":[[2004,5,4]],"date-time":"2004-05-04T18:00:58Z","timestamp":1083693658000},"page":"530-538","source":"Crossref","is-referenced-by-count":62,"title":["Head and neck tumor sites differ in prevalence and spectrum of <i>p53<\/i> alterations but these have limited prognostic value"],"prefix":"10.1002","volume":"111","author":[{"given":"Franz X.","family":"Bosch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Ritter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christel","family":"Enders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christa","family":"Flechtenmacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Abel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Dietz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Hergenhahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagen","family":"Weidauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,5,4]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.42.1.7"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1905840"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0964-1955(95)00095-X"},{"key":"e_1_2_6_5_2","first-page":"4855","article-title":"Mutations 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