title: Impact of CD68/(CD3+CD20) ratio at the invasive front of primary tumors on distant metastasis development in breast cancer.
abstract: Tumors are infiltrated by macrophages, T and B-lymphocytes, which may favor tumor development by promoting angiogenesis, growth and invasion. The aim of this study was to investigate the clinical relevance of the relative amount of macrophages (CD68⁺), T-cells (CD3⁺ and B-cells (CD20⁺) at the invasive front of breast carcinomas, and the expression of matrix metalloproteases (MMPs) and their inhibitors (TIMPs) either at the invasive front or at the tumor center. We performed an immunohistochemical study counting CD3, CD20 and CD68 positive cells at the invasive front, in 102 breast carcinomas. Also, tissue sections were stained with MMP-2, -9, -11, -14 and TIMP-2 antibodies, and immunoreactivity location, percentage of reactive area and intensity were determined at the invasive front and at the tumor center. The results showed that an increased CD68 count and CD68/(CD3+CD20) ratio were directly associated with both MMP-11 and TIMP-2 expression by mononuclear inflammatory cells at the tumor center (p = 0.041 and p = 0.025 for CD68 count and p = 0.001 and p = 0.045 for ratio, respectively for MMP-11 and TIMP-2). In addition, a high CD68/(CD3+CD20) ratio (>0.05) was directly associated with a higher probability of shortened relapse-free survival. Multivariate analysis revealed that CD68/(CD3+CD20) ratio was an independent factor associated with distant relapse-free survival (RR: 2.54, CI: (1.23-5.24), p<0.01). Therefore, CD68/(CD3+CD20) ratio at the invasive front could be used as an important prognostic marker.
authors.affiliation: Unidad de Investigación, Fundación Hospital de Jove, Gijón, Asturias, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Eiró
authors.forename: Iván
authors.initials: I
authors.lastname: Pidal
authors.forename: Belen
authors.initials: B
authors.lastname: Fernandez-Garcia
authors.forename: Sara
authors.initials: S
authors.lastname: Junquera
authors.forename: Maria L
authors.initials: ML
authors.lastname: Lamelas
authors.forename: José M
authors.initials: JM
authors.lastname: del Casar
authors.forename: Luis O
authors.initials: LO
authors.lastname: González
authors.forename: Alfonso
authors.initials: A
authors.lastname: López-Muñiz
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Vizoso
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D018951:Antigens, CD20 / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D017252:CD3 Complex / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000556:secondary*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D018951:Antigens, CD20; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D017252:CD3 Complex; D053505:Matrix Metalloproteinases, Secreted; D019716:Tissue Inhibitor of Metalloproteinase-2; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C560823:TIMP2 protein, human