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 studi...

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Autores principales: Schillaci, R., Guzmán, P., Cayrol, F., Beguelin, W., Díaz Flaqué, M.C., Proietti, C.J., Pineda, V., Palazzi, J., Frahm, I., Charreau, E.H., Maronna, E., Roa, J.C., Elizalde, P.V.
Formato: JOUR
Materias:
epidermal growth factor receptor 2
steroid receptor
tumor marker
membrane protein
nuclear protein
accuracy
adolescent
adult
article
breast carcinoma
cancer grading
cancer invasion
cancer prognosis
cancer staging
cancer survival
cellular distribution
clinical evaluation
cohort analysis
controlled study
disease association
female
histopathology
human
human tissue
immunofluorescence test
immunohistochemistry
major clinical study
outcome assessment
overall survival
primary tumor
process development
protein expression
protein function
protein localization
risk assessment
sensitivity and specificity
signal transduction
tissue microarray
tumor volume
aged
breast tumor
carcinoma
chemistry
Chile
Kaplan Meier method
metabolism
microarray analysis
middle aged
prognosis
proportional hazards model
Adult
Aged
Breast Neoplasms
Carcinoma
Cohort Studies
Female
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Membrane Proteins
Microarray Analysis
Middle Aged
Nuclear Proteins
Prognosis
Proportional Hazards Models
Receptor, erbB-2
Tumor Markers, Biological
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_14712407_v12_n_p_Schillaci
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario: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. © 2012 Schillaci et al; BioMed Central Ltd.

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