{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T14:20:16Z","timestamp":1780928416830,"version":"3.54.1"},"reference-count":52,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2013,4,12]],"date-time":"2013-04-12T00:00:00Z","timestamp":1365724800000},"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":[[2013,7,15]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Uterine serous carcinoma (USC) is a subtype of endometrial cancer associated with chemoresistance and poor outcome. Overexpression of tubulin\u2010\u03b2\u2010III and p\u2010glycoprotein has been linked to paclitaxel resistance in many cancers but has been undercharacterized among USCs. Epothilones have demonstrated activity in certain paclitaxel\u2010resistant malignancies. In this study, relationships are clarified, in USCs relative to ovarian serous carcinomas (OSCs), between tubulin\u2010\u03b2\u2010III and p\u2010glycoprotein expression, clinical outcome, and in vitro chemoresponsiveness to epothilone B, ixabepilone, and paclitaxel.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Tubulin\u2010\u03b2\u2010III and p\u2010glycoprotein were quantified by real\u2010time polymerase chain reaction in 48 fresh\u2010frozen tissue samples and 13 cell lines. Copy number was correlated with immunohistochemistry and overall survival. Median inhibitory concentration (IC<jats:sub>50<\/jats:sub>) was determined using viability and metabolic assays. Impact of tubulin\u2010\u03b2\u2010III knockdown on IC<jats:sub>50<\/jats:sub> was assessed with small interfering RNAs.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>USC overexpressed tubulin\u2010\u03b2\u2010III but not p\u2010glycoprotein relative to OSC in both fresh\u2010frozen tissues (552.9\u2009\u00b1\u2009106.7 versus 202.0\u2009\u00b1\u200943.99, <jats:italic>P<\/jats:italic>\u2009=\u2009.01) and cell lines (1701.0\u2009\u00b1\u2009376.4 versus 645.1\u2009\u00b1\u2009157.9, <jats:italic>P<\/jats:italic>\u2009=\u2009.02). Tubulin\u2010\u03b2\u2010III immunohistochemistry reflected quantitative real\u2010time polymerase chain reaction copy number and overexpression stratified patients by overall survival (copy number\u2009\u2264\u2009400: 615 days; copy number\u2009&gt;\u2009400: 165 days, <jats:italic>P<\/jats:italic>\u2009=\u2009.049); p\u2010glycoprotein did not predict clinical outcome. USCs remained exquisitely sensitive to patupilone in vitro despite tubulin\u2010\u03b2\u2010III overexpression (IC<jats:sub>50,USC<\/jats:sub> 0.245\u2009\u00b1\u20090.11 nM versus IC<jats:sub>50,OSC<\/jats:sub> 1.01\u2009\u00b1\u20090.13 nM, <jats:italic>P<\/jats:italic>\u2009=\u2009.006).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Tubulin\u2010\u03b2\u2010III overexpression in USCs discriminates poor prognosis, serves as a marker for sensitivity to epothilones, and may contribute to paclitaxel resistance. Immunohistochemistry reliably identifies tumors with overexpression of tubulin\u2010\u03b2\u2010III, and a subset of individuals likely to respond to patupilone and ixabepilone. Epothilones warrant clinical investigation for treatment of USCs. <jats:bold><jats:italic>Cancer<\/jats:italic> 2013;119:2582\u20132592<\/jats:bold>. \u00a9 <jats:italic>2013 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.28017","type":"journal-article","created":{"date-parts":[[2013,4,12]],"date-time":"2013-04-12T14:22:43Z","timestamp":1365776563000},"page":"2582-2592","source":"Crossref","is-referenced-by-count":41,"title":["Tubulin\u2010\u03b2\u2010III overexpression by uterine serous carcinomas is a marker for poor overall survival after platinum\/taxane chemotherapy and sensitivity to epothilones"],"prefix":"10.1002","volume":"119","author":[{"given":"Dana M.","family":"Roque","sequence":"first","affiliation":[{"name":"Division of Gynecologic Oncology Department of Obstetrics, Gynecology, and Reproductive Sciences Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Bellone","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology Department of Obstetrics, Gynecology, and Reproductive Sciences Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana P.","family":"English","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology Department of Obstetrics, Gynecology, and Reproductive Sciences Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Buza","sequence":"additional","affiliation":[{"name":"Department of Pathology Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiliano","family":"Cocco","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology Department of Obstetrics, Gynecology, and Reproductive Sciences Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Gasparrini","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology Department of Obstetrics, Gynecology, and Reproductive Sciences Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ileana","family":"Bortolomai","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology Department of Obstetrics, Gynecology, and Reproductive Sciences Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Ratner","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology Department of Obstetrics, Gynecology, and Reproductive Sciences Yale University School of Medicine New Haven 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