Expression of Endoplasmic Reticulum Stress Proteins Is a Candidate Marker of Brain Metastasis in both ErbB-2+ and ErbB-2− Primary Breast Tumors

open here please ►Expression of Endoplasmic Reticulum Stress Proteins Is a Candidate Marker of Brain Metastasis in both ErbB-2+ and ErbB-2− Primary Breast Tumors: "Expression of Endoplasmic Reticulum Stress Proteins Is a Candidate Marker of Brain Metastasis in both ErbB-2+ and ErbB-2− Primary Breast Tumors

* Rebeca Sanz-Pamplona
Affiliations
o Biological Clues of the Invasive and Metastatic Phenotype Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
* , Ramón Aragüés
Affiliations
o Structural Bioinformatics Group (GRIB-IMIM), University Pompeu Fabra, Barcelona, Spain
* , Keltouma Driouch
Affiliations
o INSERM U735, Centre René Huguenin, St. Cloud, France
* , Berta Martín
Affiliations
o Biological Clues of the Invasive and Metastatic Phenotype Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
* , Baldo Oliva
Affiliations
o Structural Bioinformatics Group (GRIB-IMIM), University Pompeu Fabra, Barcelona, Spain
* , Miguel Gil
Affiliations
o Medical Oncology Service, Catalan Institute of Oncology-IDIBELL, Hospital Duran i Reynals, Barcelona, Spain
* , Susana Boluda
Affiliations
o Institute of Neuropathology-Anatomic Pathology Service, IDIBELL-University Hospital of Bellvitge, Barcelona, Spain
* , Pedro L. Fernández
Affiliations
o Department of Anatomic Pathology, Clinical Hospital-IDIBAPS, University of Barcelona, Barcelona, Spain
* , Antonio Martínez
Affiliations
o Biological Clues of the Invasive and Metastatic Phenotype Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
* , Víctor Moreno
Affiliations
o Unit of Biostatistics and Bioinformatics, IDIBELL-Catalan Institute of Oncology and University of Barcelona, Barcelona, Spain
* , Juan J. Acebes
Affiliations
o Neurosurgical Service, University Hospital of Bellvitge, Barcelona, Spain
* , Rosette Lidereau
Affiliations
o INSERM U735, Centre René Huguenin, St. Cloud, France
* , Fabien Reyal
Affiliations
o CNRS UMR144, Institute Curie, Paris, France
* , Marc J. Van de Vijver
Affiliations
o Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
* , Angels Sierra
Affiliations
o Biological Clues of the Invasive and Metastatic Phenotype Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
o Corresponding Author InformationAddress reprint requests to Angels Sierra, M.D., Ph.D., Bellvitge Biomedical Research Institute-IDIBELL, Avda. Gran Via de Hospitalet Ll., 199, Hospitalet Ll., Barcelona 08908, Spain
email address

Accepted 11 April 2011. published online 27 June 2011.

The increasing incidence of breast cancer brain metastasis in patients with otherwise well-controlled systemic cancer is a key challenge in cancer research. It is necessary to understand the properties of brain-tropic tumor cells to identify patients at risk for brain metastasis. Here we attempt to identify functional phenotypes that might enhance brain metastasis. To obtain an accurate classification of brain metastasis proteins, we mapped organ-specific brain metastasis gene expression signatures onto an experimental protein-protein interaction network based on brain metastatic cells. Thirty-seven proteins were differentially expressed between brain metastases and non-brain metastases. Analysis of metastatic tissues, the use of bioinformatic approaches, and the characterization of protein expression in tumors with or without metastasis identified candidate markers. A multivariate analysis based on stepwise logistic regression revealed GRP94, FN14, and inhibin as the best combination to discriminate between brain and non-brain metastases (ROC AUC = 0.85, 95% CI = 0.73 to 0.96 for the combination of the three proteins). These markers substantially improve the discrimination of brain metastasis compared with ErbB-2 alone (AUC = 0.76, 95% CI = 0.60 to 0.93). Furthermore, GRP94 was a better negative marker (LR = 0.16) than ErbB-2 (LR = 0.42). We conclude that, in breast carcinomas, certain proteins associated with the endoplasmic reticulum stress phenotype are candidate markers of brain metastasis.

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Actualidad Ultimas noticias - JANOes y agencias - El 30 de las metastasis de cancer mamario afectan al cerebro - JANO.es - ELSEVIER: "ONCOLOGÍA
El 30% de las metástasis de cáncer mamario afectan al cerebro

JANO.es y agencias · 02 Agosto 2011 09:45


La sobreexpresión de determinadas proteínas en el tumor primario muestra la predisposición de la paciente a que la enfermedad acabe afectando al cerebro.

Investigadores del Instituto de Investigación Biomédica de Bellvitge (Idibell) han hallado diversos biomarcadores útiles para predecir el riesgo de metástasis cerebral en pacientes con cáncer de mama, una complicación que representa el 30% de las metástasis producidas por este tumor.

En un comunicado, el Idibell ha señalado que la sobreexpresión de determinadas proteínas en el tumor primario muestra la predisposición de la paciente a que la metástasis acabe afectando al cerebro, según demuestra un estudio elaborado sobre 300 muestras clínicas y cuyos resultados publica la revista The American Journal of Pathology.

Estos biomarcadores permiten la predicción del riesgo tanto en pacientes con tumores ErB2 positivos como en tumores triple negativo, por lo que su uso sería beneficioso para catalogar a ambos subgrupos, que son los que presentan mayor propensión a desarrollar metástasis cerebral.

El estudio, coordinado por la investigadora del grupo de Claves Biológicas del Fenotipo Invasivo y Metastático del Idibell, Àngels Sierra, ha contado con la financiación de la Unión Europea (UE), el Ministerio de Ciencia, el Instituto de Salud Carlos III y la Red de Bancos de Tumores de Catalunya.

Junto con el grupo del Idibell, han participado el Instituto Catalán de Oncología (ICO), el Hospital de Bellvitge y la Universitat Pompeu Fabra (UPF), además de investigadores franceses y holandeses.


The American Journal of Pathology (2011); doi:10.1016/j.ajpath.2011.04.037
Expression of Endoplasmic Reticulum Stress Proteins Is a Candidate Marker of Brain Metastasis in both ErbB-2+ and ErbB-2− Primary Breast Tumors: "- Enviado mediante la barra Google"

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