HER2 as a target in invasive urothelial carcinoma
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- dc.contributor.author Bellmunt Molins, Joaquim, 1959-ca
- dc.contributor.author Werner, Lillianca
- dc.contributor.author Bamias, Aristotleca
- dc.contributor.author Fay, André P.ca
- dc.contributor.author Park, Rachel S.ca
- dc.contributor.author Riester, Markusca
- dc.contributor.author Selvarajah, Shaminica
- dc.contributor.author Barletta, Justine A.ca
- dc.contributor.author Berman, David M.ca
- dc.contributor.author Muga, Silvia deca
- dc.contributor.author Salido, Martaca
- dc.contributor.author Gallardo, Enriqueca
- dc.contributor.author Rojo, Federicoca
- dc.contributor.author Guancial, Elizabeth A.ca
- dc.contributor.author Bambury, Richardca
- dc.contributor.author Mullane, Stephanie A.ca
- dc.contributor.author Choueiri, Toni K.ca
- dc.contributor.author Loda, Massimoca
- dc.contributor.author Stack, Edwardca
- dc.contributor.author Rosenberg, Jonathan E.ca
- dc.date.accessioned 2015-04-10T08:55:58Z
- dc.date.available 2015-04-10T08:55:58Z
- dc.date.issued 2015
- dc.description.abstract We evaluated primary tumors from two cohorts, Spain (N = 111) and Greece (N = 102), for patients who were treated with platinum-based chemotherapy. Patients were tested for HER2 status (IHC score of 3+ or FISH ratio of ≥2.2) by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), DNA copy number, mRNA expression, and mutation status in patients with metastatic urothelial carcinoma (UC), and its impact on survival. ERBB2 mutation was determined by hotspot sequencing. mRNA expression was assessed using NanoString counting. Association of overall survival (OS) and HER2 status was assessed by a Cox regression model. NIH-3T3 cells containing HER2 V777L were assessed for growth, invasion, and HER2 kinase activation. In all, 22% of Spanish and 4% of Greek cohorts had 3+ HER2 staining by IHC. FISH amplification was identified in 20% of Spanish and 4% of Greek cohorts. Kappa coefficient between FISH and IHC was 0.47. HER2 status was not associated with OS in univariate (Spanish P = 0.34; Greek P = 0.11) or multivariate (Spanish P = 0.49; Greek P = 0.12) analysis. HER2-positive tumors expressed higher levels of HER2 mRNA than HER2-negative tumors (P < 0.001). HER2 mutations (V777L and L755S) were identified in two (2%) patients. In vitro analysis of V777L results in transformation of NIH-3T3 cells, leading to increased growth, invasion on soft agar, and HER2 kinase constitutive activation. In summary, HER2 overexpression or amplification in the primary tumor did not predict OS in patients with metastatic UC. HER2 positivity rates can differ between different populations. Further trials in genomically screened patients are needed to assess HER2-targeted therapies in UCca
- dc.description.sponsorship This work has been supported by PI061513 (Spanish Health Ministry Grant “Fondo de/nInvestigacion Sanitaria”) and RTICC 06/0020/19 grants.
- dc.format.mimetype application/pdfca
- dc.identifier.citation Bellmunt J, Werner L, Bamias A, Fay AP, Park RS, Riester M, et al. HER2 as a target in invasive urothelial carcinoma. Cancer Med. 2015 Feb 26;4(6):844-52. doi: 10.1002/cam4.432.ca
- dc.identifier.doi http://dx.doi.org/10.1002/cam4.432
- dc.identifier.issn 2045-7634
- dc.identifier.uri http://hdl.handle.net/10230/23383
- dc.language.iso engca
- dc.publisher Wileyca
- dc.relation.ispartof Cancer Medicine. 2015 Feb 26;4(6):844-52
- dc.rights © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly citedca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/ca
- dc.subject.other Càncerca
- dc.subject.other Prognosica
- dc.title HER2 as a target in invasive urothelial carcinomaca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca