{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T21:48:19Z","timestamp":1772142499773,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,12,16]],"date-time":"2018-12-16T00:00:00Z","timestamp":1544918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Head &amp; Neck"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>This study investigated the hypothesis that phosphoinositide 3\u2010kinase (PI3\u2010kinase) pathway dysregulation in either head and neck cancer cells and\/or tumor infiltrating immune cells would influence outcomes of patients with surgically treated oral tongue squamous cell carcinomas (SCC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We constructed tissue microarrays containing 123 oral tongue SCC samples and performed immunohistochemistry using antibodies against 7 PI3\u2010kinase pathway markers: phosphatase and tensin homolog (PTEN), Akt, p\u2010Akt, mammalian target of rapamycin (mTOR), phosphorylated\u2010mammalian target of rapamycin (p\u2010mTOR), survivin, and Ki\u201067). Expression levels in cancer cells or tumor infiltrating immune cells were correlated with outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Higher levels of PTEN expression in immune cells were significantly associated with improved recurrence\u2010free survival (heart rate (HR)\u2009=\u20090.45, 95% confidence interval (CI) 0.23\u20100.90, <jats:italic>P<\/jats:italic>\u2009=\u2009.03), and overall survival (HR\u2009=\u20090.34, 95% CI 0.15\u20100.76, <jats:italic>P<\/jats:italic>\u2009=\u2009.01) on univariate and multicovariate models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified a novel, negative prognostic role of PI3\u2010kinase activation (as determined by PTEN loss) in oral SCC infiltrating immune cells. These findings could be relevant for clinical development of PI\u20103 kinase inhibitors for this disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hed.25350","type":"journal-article","created":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T03:38:56Z","timestamp":1545017936000},"page":"615-622","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["PI3\u2010kinase pathway biomarkers in oral cancer and tumor immune cells"],"prefix":"10.1002","volume":"41","author":[{"given":"Mohammad Y.","family":"Ibrahim","sequence":"first","affiliation":[{"name":"Seton Hall University College of Arts and Sciences, Department of Internal Medicine at St. Francis Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria I.","family":"Nunez","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Department of Pathology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nusrat","family":"Harun","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Department of Biostatistics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Jack","family":"Lee","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Department of Biostatistics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adel K.","family":"El\u2010Naggar","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Department of Pathology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata","family":"Ferrarotto","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Department of Thoracic\/Head and Neck Medical Oncology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignacio","family":"Wistuba","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Department of Pathology"},{"name":"The University of Texas MD Anderson Cancer Center, Department of Translational Molecular Pathology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Myers","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Head and Neck Surgery  Houston TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bonnie S.","family":"Glisson","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Department of Thoracic\/Head and Neck Medical Oncology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"William N.","family":"William","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Department of Thoracic\/Head and Neck Medical Oncology"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,12,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.07.029"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14129"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12206"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.121024"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2015.00166"},{"issue":"24","key":"e_1_2_7_7_1","first-page":"7350","article-title":"Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma","volume":"62","author":"Kian Ang K","year":"2002","journal-title":"Cancer Res."},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.127.12.1441"},{"key":"e_1_2_7_9_1","doi-asserted-by":"crossref","unstructured":"LiY WangJ WangF et al. 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