Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer

BMC Cancer

Research Article

Pablo Guzmán¹  Juan C Roa¹  Viviana Pineda²  Florencia Cayrol³  Wendy Beguelin³  Roxana Schillaci³  María C Díaz Flaqué³  Cecilia J Proietti³  Eduardo H Charreau³  Patricia V Elizalde⁴  Esteban Maronna⁵  Isabel Frahm⁵  Jorge Palazzi⁶ 

[1] Departamento de Anatomía Patológica (BIOREN) y, Universidad de La Frontera, Temuco, Chile;Departamento de Cirugía, Facultad de Medicina, Universidad de La Frontera, Temuco, Chile;Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina;Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina;Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME), Obligado 2490, Buenos Aires 1428, Argentina;Servicio de Patología, Sanatorio Mater Dei, Buenos Aires, Argentina;Universidad Abierta Interamericana (UAI), Rosario, Argentina;

关键词: Overall Survival;    Trastuzumab;    Progesterone Receptor;    Molecular Subtype;    A0485 Antibody;   

DOI  :  10.1186/1471-2407-12-74

 received in 2011-11-03, accepted in 2012-02-22,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe biological relevance of nuclear ErbB-2/HER2 (NuclErbB-2) presence in breast tumors remains unexplored. In this study we assessed the clinical significance of ErbB-2 nuclear localization in primary invasive breast cancer. The reporting recommendations for tumor marker prognostic studies (REMARK) guidelines were used as reference.MethodsTissue microarrays from a cohort of 273 primary invasive breast carcinomas from women living in Chile, a Latin American country, were examined for membrane (MembErbB-2) and NuclErbB-2 expression by an immunofluorescence (IF) protocol we developed. ErbB-2 expression was also evaluated by immunohistochemistry (IHC) with a series of antibodies. Correlation between NuclErbB-2 and MembErbB-2, and between NuclErbB-2 and clinicopathological characteristics of tumors was studied. The prognostic value of NuclErbB-2 in overall survival (OS) was evaluated using Kaplan-Meier method, and Cox model was used to explore NuclErbB-2 as independent prognostic factor for OS.ResultsThe IF protocol we developed showed significantly higher sensitivity for detection of NuclErbB-2 than IHC procedures, while its specificity and sensitivity to detect MembErbB-2 were comparable to those of IHC procedures. We found 33.6% NuclErbB-2 positivity, 14.2% MembErbB-2 overexpression by IF, and 13.0% MembErbB-2 prevalence by IHC in our cohort. We identified NuclErbB-2 positivity as a significant independent predictor of worse OS in patients with MembErbB-2 overexpression. NuclErbB-2 was also a biomarker of lower OS in tumors that overexpress MembErbB-2 and lack steroid hormone receptors.ConclusionsWe revealed a novel role for NuclErbB-2 as an independent prognostic factor of poor clinical outcome in MembErbB-2-positive breast tumors. Our work indicates that patients presenting NuclErbB-2 may need new therapeutic strategies involving specific blockage of ErbB-2 nuclear migration.

【 授权许可】

Unknown   
© Schillaci et al; BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.