title: Down regulation of ADAM33 as a Predictive Biomarker of Aggressive Breast Cancer.
abstract: Breast cancer is a heterogeneous disease with differences in its clinical, molecular and biological features. Traditionally, immunohistochemical markers together with clinicopathologic parameters are used to classify breast cancer and to predict disease outcome. Triple-negative breast cancer (TNBC) is a particular type of breast cancer that is defined by a lack of expression of hormonal receptors and the HER2 gene. Most cases of TNBC also have a basal-like phenotype (BLBC) with expression of cytokeratin 5/6 and/or EGFR. A basal marker alone is insufficient for a better understanding of the tumor biology of TNBC. In that regard, the ADAM33 gene is silenced by DNA hypermethylation in breast cancer, which suggests that ADAM33 might be useful as a molecular marker. In the present study, we have produced monoclonal antibodies against the ADAM33 protein and have investigated the role of ADAM33 protein in breast cancer. We used 212 breast tumor samples and lower levels of ADAM33 were correlated with TNBC and basal-like markers. A lower level of ADAM33 was also correlated with shorter overall survival and metastasis-free survival and was considered an independent prognostic factor suggesting that ADAM33 is a novel molecular biomarker of TNBC and BLBC that might be useful as a prognostic factor.
authors.affiliation: Department of Basic Pathology, Federal University of Parana, Curitiba, Paraná, Brazil.
authors.forename: Graciele C M
authors.initials: GC
authors.lastname: Manica
authors.affiliation: Department of Basic Pathology, Federal University of Parana, Curitiba, Paraná, Brazil.
authors.forename: Caroline F
authors.initials: CF
authors.lastname: Ribeiro
authors.affiliation: Department of Biochemistry, State University of Maringa, Maringa, Brazil.
authors.forename: Marco A S de
authors.initials: MA
authors.lastname: Oliveira
authors.affiliation: Department of Basic Pathology, Federal University of Parana, Curitiba, Paraná, Brazil.
authors.forename: Isabela T
authors.initials: IT
authors.lastname: Pereira
authors.affiliation: Department of Basic Pathology, Federal University of Parana, Curitiba, Paraná, Brazil.
authors.forename: Andressa
authors.initials: A
authors.lastname: Chequin
authors.affiliation: Department of Basic Pathology, Federal University of Parana, Curitiba, Paraná, Brazil.
authors.forename: Edneia A S
authors.initials: EA
authors.lastname: Ramos
authors.affiliation: Department of Basic Pathology, Federal University of Parana, Curitiba, Paraná, Brazil.
authors.forename: Liliane M B
authors.initials: LM
authors.lastname: Klassen
authors.affiliation: Department of Medical Pathology, Federal University of Parana, Curitiba, Parana, Brazil.
authors.forename: Ana Paula M
authors.initials: AP
authors.lastname: Sebastião
authors.affiliation: Department of Basic Pathology, Federal University of Parana, Curitiba, Paraná, Brazil.
authors.forename: Larissa M
authors.initials: LM
authors.lastname: Alvarenga
authors.affiliation: Department of Basic Pathology, Federal University of Parana, Curitiba, Paraná, Brazil.
authors.forename: Silvio M
authors.initials: SM
authors.lastname: Zanata
authors.affiliation: School of Medicine, Pontifical Catholic University of Parana, Curitiba, Paraná, Brazil.
authors.forename: Lucia De
authors.initials: L
authors.lastname: Noronha
authors.affiliation: Department of Tocogynecology, Federal University of Parana, Curitiba, Parana, Brazil.
authors.forename: Iris
authors.initials: I
authors.lastname: Rabinovich
authors.affiliation: Genomic Sciences and Biotechnology Program, University Catholic of Brasilia, DF, Brazil.
authors.forename: Fabricio F
authors.initials: FF
authors.lastname: Costa
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Parana, Curitiba, Parana, Brazil.
authors.forename: Emanuel M
authors.initials: EM
authors.lastname: Souza
authors.affiliation: Department of Basic Pathology, Federal University of Parana, Curitiba, Paraná, Brazil.
authors.forename: Giseli
authors.initials: G
authors.lastname: Klassen
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D061986:MCF-7 Cells; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D064726:Triple Negative Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
chemical_list: D051722:ADAM Proteins; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C450441:ADAM33 protein, human