{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:33:52Z","timestamp":1789979632942,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2002,10,25]],"date-time":"2002-10-25T00:00:00Z","timestamp":1035504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2002,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Numerous reports have documented a direct involvement of matrix metalloproteinase (MMP) overexpression in the development and progression of head and neck squamous cell carcinoma (HNSCC). In this study, the authors examined whether the expression of MMPs in HNSCC is correlated with other steps involved in tumor growth and metastasis, like angiogenesis, activation the nitric oxide (NO) pathway, and alteration of the <jats:italic>p53<\/jats:italic> tumor suppressor gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>MMP\u20101, MMP\u20102, and MMP\u20109 expression levels were examined immunohistochemically in samples from 43 patients with HNSCC. Microvessel density (MVD) was determined by immunostaining of endothelial cells with anti\u2010CD31 monoclonal antibody. Inducible nitric oxide synthase (iNOS) activity and cyclic guanosine monophosphatate (cGMP) levels were assessed in fresh tumor samples, whereas exons 5\u20139 of the <jats:italic>p53<\/jats:italic> gene were analyzed by reverse transcriptase\u2010polymerase chain reaction, single\u2010strand conformation polymorphism analysis and were sequenced.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>MMP\u20101 overexpression (&gt;10% of tumor cells) was identified in 32 tumors (74.5%), whereas elevated levels of MMP\u20102 and MMP\u20109 were detected in 17 tumors (39.5%) each. Tumors with MMP\u20109 overexpression were characterized by significantly higher MVD (<jats:italic>P<\/jats:italic> = 0.05) and significantly higher iNOS activity and cGMP levels (<jats:italic>P<\/jats:italic> = 0.005 and <jats:italic>P<\/jats:italic> = 0.02, respectively). Moreover, <jats:italic>p53<\/jats:italic> mutation was associated strongly with MMP\u20109 overexpression (<jats:italic>P<\/jats:italic> = 0.004). Conversely, no correlation was found between MMP\u20101 and MMP\u20102 expression, angiogenesis, iNOS activity, cGMP levels, and <jats:italic>p53<\/jats:italic> mutation in this series.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>This study documents the existence of a correlation between MMP\u20109 expression, activity of the iNOS pathway, <jats:italic>p53<\/jats:italic> status, and angiogenesis in patients with HNSCC. This raises the possibility that <jats:italic>p53<\/jats:italic> mutation, which frequently is present in HNSCC, may result in increased angiogenesis and invasiveness related to increased nitric oxide and MMP production by tumor cells, ultimately contributing to tumor progression. Cancer 2002;95:1902\u201310. \u00a9 2002 American Cancer Society.<\/jats:p><jats:p>DOI 10.1002\/cncr.10916<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.10916","type":"journal-article","created":{"date-parts":[[2002,10,29]],"date-time":"2002-10-29T08:57:53Z","timestamp":1035881873000},"page":"1902-1910","source":"Crossref","is-referenced-by-count":110,"title":["Expression of matrix metalloproteinase 1, matrix metalloproteinase 2, and matrix metalloproteinase 9 in carcinoma of the head and 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