{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:10:18Z","timestamp":1790165418386,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,10,9]],"date-time":"2008-10-09T00:00:00Z","timestamp":1223510400000},"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":[[2009,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Wnt pathway signaling is crucial in many cancers and data indicate crosstalk with other key cancer pathways, however in urothelial carcinogenesis it has not been extensively studied. We searched for mutations in adenomatous polyposis coli (APC), a key regulator of the pathway, and studied b\u2010catenin expression and interactions with the expression of other markers of apoptosis, angiogenesis, and proliferation in patients with invasive urothelial cancer. The mutation cluster region of APC was directly sequenced in 70 patients with muscle invasive disease who were treated with surgery and adjuvant chemotherapy. COX\u20102, p53, Ki67, and b\u2010catenin were studied immunohistochemically and micro vessel density was quantified by CD105 expression. Single somatic amino\u2010acid substitutions (missense) were found in 9 (13%) and frameshift deletions in 2 (3%) tumors, all located in regions adjacent to b\u2010catenin binding sites. Patients having either APC missense mutations or b\u2010catenin nuclear accumulation had less frequent COX\u20102 overexpression (24% vs. 76%, <jats:italic>p<\/jats:italic> = 0.043) and more frequent lymph node involvement (75% vs. 38%, <jats:italic>p<\/jats:italic> = 0.023). Patients with either APC mutations or b\u2010catenin accumulation had shorter disease\u2010free interval (13.4 vs. 28 months, <jats:italic>p<\/jats:italic> = 0.07), whereas in multivariate analysis they had shorter disease\u2010specific survival (60.5 vs. 20.6 months, <jats:italic>p<\/jats:italic> = 0.048). Somatic APC missense mutations are not rare in advanced urothelial neoplasms. Either APC mutations and\/or aberrant expression of b\u2010catenin are associated with worse outcome. Further study of the role of the Wnt pathway, potential crosstalk with other pathways and potential candidate therapeutic targets in urothelial cancer is needed. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.23917","type":"journal-article","created":{"date-parts":[[2008,10,9]],"date-time":"2008-10-09T14:57:22Z","timestamp":1223564242000},"page":"103-108","source":"Crossref","is-referenced-by-count":50,"title":["Somatic mutations of adenomatous polyposis coli gene and nuclear b\u2010catenin accumulation have prognostic significance in invasive urothelial carcinomas: Evidence for Wnt pathway implication"],"prefix":"10.1002","volume":"124","author":[{"given":"Efstathios","family":"Kastritis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Murray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fani","family":"Kyriakou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Horti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaos","family":"Tamvakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaos","family":"Kavantzas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efstratios 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