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

Background The 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. Methods Tissue 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. Results The 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. Conclusions We 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..

Media Type:

Electronic Article

Year of Publication:

2012

Publication:

2012

Contained In:

To Main Record - volume:12

Contained In:

BMC cancer - 12(2012), 1 vom: 22. Feb.

Language:

English

Contributors:

Schillaci, Roxana [Author]
Guzmán, Pablo [Author]
Cayrol, Florencia [Author]
Beguelin, Wendy [Author]
Díaz Flaqué, María C [Author]
Proietti, Cecilia J [Author]
Pineda, Viviana [Author]
Palazzi, Jorge [Author]
Frahm, Isabel [Author]
Charreau, Eduardo H [Author]
Maronna, Esteban [Author]
Roa, Juan C [Author]
Elizalde, Patricia V [Author]

Links:

Volltext [kostenfrei]

Keywords:

A0485 Antibody
Molecular Subtype
Overall Survival
Progesterone Receptor
Trastuzumab

Notes:

© 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 (

doi:

10.1186/1471-2407-12-74

funding:

Supporting institution / Project title:

PPN (Catalogue-ID):

SPR02763731X