{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:27:58Z","timestamp":1791329278531,"version":"4.3.1"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,12,17]],"date-time":"2012-12-17T00:00:00Z","timestamp":1355702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mucinous ovarian carcinomas (<jats:styled-content style=\"fixed-case\">MCs<\/jats:styled-content>) typically do not respond to current conventional therapy. We have previously demonstrated amplification of <jats:italic><jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content><\/jats:italic> in 6 of 33 (18.2%) mucinous ovarian carcinomas (<jats:styled-content style=\"fixed-case\">MCs<\/jats:styled-content>) and presented anecdotal evidence of response with <jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content>\u2010targeted treatment in a small series of women with recurrent <jats:italic><jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content><\/jats:italic>\u2010amplified (<jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content>+) <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>. Here, we explore <jats:italic><jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content><\/jats:italic> amplification and <jats:italic><jats:styled-content style=\"fixed-case\">KRAS<\/jats:styled-content><\/jats:italic> mutation status in an independent cohort of 189 <jats:styled-content style=\"fixed-case\">MCs<\/jats:styled-content> and 199 mucinous borderline ovarian tumours (<jats:styled-content style=\"fixed-case\">MBOTs<\/jats:styled-content>) and their association to clinicopathological features. <jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content> status was assessed by immunohistochemistry (<jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content>), <jats:styled-content style=\"fixed-case\">FISH<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">CISH<\/jats:styled-content>, and interpreted per <jats:styled-content style=\"fixed-case\">ASCO<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">CAP<\/jats:styled-content> guidelines, with intratumoural heterogeneity assessment on full sections, where available. <jats:italic><jats:styled-content style=\"fixed-case\">KRAS<\/jats:styled-content><\/jats:italic> mutation testing was performed with Sanger sequencing. Stage and grade were associated with recurrence on both univariate and multivariate analysis (<jats:italic>p<\/jats:italic> &lt; 0.001). Assessment of <jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content> status revealed overexpression\/amplification of <jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content> in 29\/154 (18.8%) <jats:styled-content style=\"fixed-case\">MCs<\/jats:styled-content> and 11\/176 (6.2%) <jats:styled-content style=\"fixed-case\">MBOTs<\/jats:styled-content>. There was excellent agreement between <jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">FISH<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">CISH<\/jats:styled-content> assessment of <jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content> status (perfect concordance of <jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content> 0 or 1+ <jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content> with non\u2010amplified status, and 3+ <jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content> with amplified status). <jats:italic><jats:styled-content style=\"fixed-case\">KRAS<\/jats:styled-content><\/jats:italic> mutations were seen in 31\/71 (43.6%) <jats:styled-content style=\"fixed-case\">MCs<\/jats:styled-content> and 26\/33 (78.8%) <jats:styled-content style=\"fixed-case\">MBOTs<\/jats:styled-content>, and were near mutually exclusive of <jats:italic><jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content><\/jats:italic> amplification. In the 189 <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content> cases, a total of 54 recurrences and 59 deaths (53 of progressive disease) were observed. Within <jats:styled-content style=\"fixed-case\">MCs<\/jats:styled-content>, either <jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content> amplification\/overexpression or <jats:italic><jats:styled-content style=\"fixed-case\">KRAS<\/jats:styled-content><\/jats:italic> mutation was associated with decreased likelihood of disease recurrence (<jats:italic>p<\/jats:italic> = 0.019) or death (<jats:italic>p<\/jats:italic> = 0.0041) when compared to cases with neither feature. Intratumoural heterogeneity was noted in 26% of <jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content>\u2010overexpressing cases. These data support the stratification of <jats:styled-content style=\"fixed-case\">MCs<\/jats:styled-content> for the testing of new treatments, with <jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content>\u2010targeted therapy as a viable option for <jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content>+ advanced or recurrent disease. Further research is required to delineate the molecular and clinical features of the \u223c34% of <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content> cases with neither <jats:italic><jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content><\/jats:italic> amplification nor <jats:italic><jats:styled-content style=\"fixed-case\">KRAS<\/jats:styled-content><\/jats:italic> mutations.<\/jats:p>","DOI":"10.1002\/path.4088","type":"journal-article","created":{"date-parts":[[2012,8,16]],"date-time":"2012-08-16T06:03:16Z","timestamp":1345096996000},"page":"111-120","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":180,"title":["Molecular characterization of mucinous ovarian tumours supports a stratified treatment approach with <scp>HER2<\/scp> targeting in 19% of carcinomas"],"prefix":"10.1002","volume":"229","author":[{"given":"Michael 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