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

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spelling	todo:paper_14712407_v12_n_p_Schillaci2023-10-03T16:17:53Z Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer 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. epidermal growth factor receptor 2 steroid receptor tumor marker epidermal growth factor receptor 2 membrane protein nuclear protein tumor marker 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 Chile 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_14712407_v12_n_p_Schillaci
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	epidermal growth factor receptor 2 steroid receptor tumor marker epidermal growth factor receptor 2 membrane protein nuclear protein tumor marker 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 Chile 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
spellingShingle	epidermal growth factor receptor 2 steroid receptor tumor marker epidermal growth factor receptor 2 membrane protein nuclear protein tumor marker 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 Chile 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 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. Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer
topic_facet	epidermal growth factor receptor 2 steroid receptor tumor marker epidermal growth factor receptor 2 membrane protein nuclear protein tumor marker 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 Chile 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
description	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.
format	JOUR
author	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.
author_facet	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.
author_sort	Schillaci, R.
title	Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer
title_short	Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer
title_full	Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer
title_fullStr	Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer
title_full_unstemmed	Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer
title_sort	clinical relevance of erbb-2/her2 nuclear expression in breast cancer
url	http://hdl.handle.net/20.500.12110/paper_14712407_v12_n_p_Schillaci
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Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer

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