{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:44:26Z","timestamp":1786977866762,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,6,10]],"date-time":"2011-06-10T00:00:00Z","timestamp":1307664000000},"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":[[2012,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Diffuse overexpression of p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    in basal and parabasal cells of cervical epithelium is a hallmark of human papillomavirus\u2010mediated transformation. Focal p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    expression is occasionally observed in nondysplastic epithelium. In normal cells, expression of p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    triggers cell cycle arrest. However, cells undergoing transformation in intraepithelial lesions actively proliferate. To prove that the different expression patterns of p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    ,\n                    <jats:italic>i.e.<\/jats:italic>\n                    , focal\n                    <jats:italic>versus<\/jats:italic>\n                    diffuse, reflect biologically different entities, we hypothesized that p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    \u2010positive cells in epithelia displaying focal p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    expression pattern do not coexpress proliferation\u2010associated Ki\u201067 protein, while p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    \u2010positive cells in lesions with diffuse p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    expression may do. A total of 138 cervical cone biopsies were stained for the expression of p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    and Ki\u201067 using a primary antibody cocktail. All metaplastic lesions (\n                    <jats:italic>n<\/jats:italic>\n                    = 21) displayed focal staining for p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    , and in all of these lesions p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    \u2010positive cells were found to be negative for Ki\u201067 expression. Diffuse expression of p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    was observed in 12\/21 (57.1%) cervical intraepithelial neoplasia (CIN) 1 lesions, all of them simultaneously showed Ki\u201067 immunoreactivity in a large proportion of p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    \u2010positive cells. Seventeen of 23 (73.9%) CIN2 lesions and all 27 (100%) CIN3\/carcinoma in situ (CIS) as well as all 46 (100%) carcinoma cases displayed diffuse and combined expression of p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    and Ki\u201067. Coexpression of Ki\u201067 and p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    in the same cell is entirely restricted to cervical lesions displaying diffuse p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    expression, whereas in lesions with focal p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    expression, p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    \u2010expressing cells are negative for Ki\u201067. Thus, diffuse expression of p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    reflects lesions with proliferation\u2010competent cells, while p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    \u2010expressing cells associated with focal expression patterns are cell cycle arrested.\n                  <\/jats:p>","DOI":"10.1002\/ijc.26017","type":"journal-article","created":{"date-parts":[[2011,3,8]],"date-time":"2011-03-08T10:45:31Z","timestamp":1299581131000},"page":"388-394","source":"Crossref","is-referenced-by-count":60,"title":["Evaluation of cervical cone biopsies for coexpression of p16\n                    <sup>INK4a<\/sup>\n                    and Ki\u201067 in epithelial cells"],"prefix":"10.1002","volume":"130","author":[{"given":"Miriam","family":"Reuschenbach","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"Seiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina von Knebel","family":"Doeberitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Vinokurova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Duwe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruediger","family":"Ridder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Sartor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich","family":"Kommoss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus von Knebel","family":"Doeberitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,6,10]]},"reference":[{"key":"e_1_2_5_2_2","unstructured":"Ferlay J Shin HR Bray F Forman D Mathers C and Parkin DM. 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