title: Human epidermal growth factor receptor 2, Na+/H+ exchanger regulatory factor 1, and breast cancer susceptibility gene-1 as new biomarkers for familial breast cancers.
abstract: The aim of this study is to evaluate the analysis of markers related with progression, to further characterize familial breast cancers. Here, we investigated the expression of breast cancer susceptibility gene-1, hypoxia-inducible factor-1α, vascular endothelial growth factor receptor 1, and Na+/H+ exchanger regulatory factor 1 in 187 microarrayed breast carcinomas from 94 familial and 93 sporadic breast cancer patients by immunohistochemical staining. Furthermore, the expression levels of these biomarkers were compared with triple-negative phenotype. Familiarity was significantly associated with younger age (P < .000), higher tumor grade (P = .038), negative estrogen receptor hormonal status (P = .036), and high proliferative activity (P = .029). The familial cancers were immunonegative for membranous Na+/H+ exchanger regulatory factor 1 expression compared with sporadic cancers (P = .001); notably, vascular endothelial growth factor receptor 1 staining correlated with cytoplasmic Na+/H+ exchanger regulatory factor 1 expression in familial tumors (P = .009). In multivariate analysis, the "new biomarkers," including negative human epidermal growth factor receptor 2 status (odds ratio, 4.538; 95% confidence interval, 1.756-11.728), negative membranous Na+/H+ exchanger regulatory factor 1 expression (odds ratio, 7.686; 95% confidence interval, 1.876-31.483) and positive nuclear breast cancer susceptibility gene-1 (odds ratio, 0.3982; 95% confidence interval, 0.169-0.936), significantly correlated with family history of breast cancer. We hypothesize that the evaluation of human epidermal growth factor receptor 2, Na+/H+ exchanger regulatory factor 1, and breast cancer susceptibility gene-1 could be clinically useful to identify familial breast tumors and to select patients candidate to breast cancer susceptibility genes 1/2 gene sequencing.
authors.affiliation: Clinical Experimental Oncology Laboratory, National Cancer Centre, Viale Orazio Flacco, 65-70124 Bari, Italy. a.mangia@oncologico.bari.it
authors.forename: Annita
authors.initials: A
authors.lastname: Mangia
authors.forename: Andrea
authors.initials: A
authors.lastname: Malfettone
authors.forename: Concetta
authors.initials: C
authors.lastname: Saponaro
authors.forename: Stefania
authors.initials: S
authors.lastname: Tommasi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Simone
authors.forename: Angelo
authors.initials: A
authors.lastname: Paradiso
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005192:Family Health; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D007150:Immunohistochemistry; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics*; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor; D066246:ErbB Receptors