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However, it remains unknown how such a neoplastic stroma is actually arranged in tumor tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To this end, tissue microarray samples, in which keratin and perlecan were contrastively labeled by immunohistochemistry, were three\u2010dimensionally analyzed using digital images and image analysis software to demonstrate the relationship between <jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content> foci and the perlecan\u2010positive stromal space or that between carcinoma in situ (<jats:styled-content style=\"fixed-case\">CIS<\/jats:styled-content>) and invasive <jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content> foci.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The three\u2010dimensional (3D) reconstruction demonstrated three kinds of perlecan profiles for inside (I) and outside (O) areas of the carcinoma cell focus: mode 1, I<jats:sup>+<\/jats:sup>\/O<jats:sup>\u2212<\/jats:sup>; mode 2, I<jats:sup>+<\/jats:sup>\/O<jats:sup>+<\/jats:sup>; and mode 3, I<jats:sup>\u2212<\/jats:sup>\/O<jats:sup>+<\/jats:sup>. Mode 1 was seen in <jats:styled-content style=\"fixed-case\">CIS<\/jats:styled-content> as well as <jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content> tumor massifs in the surface part. Mode 2 was seen in small <jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content> foci, which seemed isolated in 2D sections but were mostly continuous with the tumor massif in 3D reconstructions. Mode 3 was limited to small <jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content> foci, which were truly segregated from the tumor massif.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results indicated that the 2D <jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content> focus isolation could not be regarded as invasion but that the <jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content> foci surrounded by perlecan\u2010positive stroma (modes 2 and 3) could be regarded as a more objective measure for invasion of <jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content>. This is the first 3D tissue\u2010level demonstration of the neoplastic stroma space induced with oral <jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content> invasion, the presence of which we have predicted based on our previous 2D and tissue culture evidence.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jop.12184","type":"journal-article","created":{"date-parts":[[2014,4,4]],"date-time":"2014-04-04T09:54:45Z","timestamp":1396605285000},"page":"627-636","source":"Crossref","is-referenced-by-count":10,"title":["Three\u2010dimensional visualization of perlecan\u2010rich neoplastic stroma induced concurrently with the invasion of oral squamous cell carcinoma"],"prefix":"10.1111","volume":"43","author":[{"given":"Satoshi","family":"Maruyama","sequence":"first","affiliation":[{"name":"Oral Pathology Section Department of Surgical Pathology Niigata University Hospital Niigata 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