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 (CD68âº), T-cells (CD3⺠and B-cells (CD20âº) 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 (pâ=â0.041 and pâ=â0.025 for CD68 count and pâ=â0.001 and pâ=â0.045 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.
Subject(s)
Antigens, CD20/metabolism , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Breast Neoplasms/pathology , CD3 Complex/metabolism , Carcinoma, Ductal, Breast/secondary , B-Lymphocytes/metabolism , B-Lymphocytes/pathology , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Disease-Free Survival , Female , Humans , Macrophages/metabolism , Macrophages/pathology , Matrix Metalloproteinases, Secreted/metabolism , Multivariate Analysis , Neoplasm Invasiveness , Prognosis , Proportional Hazards Models , Survival Analysis , T-Lymphocytes/metabolism , T-Lymphocytes/pathology , Tissue Array Analysis , Tissue Inhibitor of Metalloproteinase-2/metabolismABSTRACT
AIMS: Matrix metalloproteases (MMPs) and their inhibitors (TIMPs) play an essential role in the degradation of stromal connective tissue and basement membrane components. The aim of this study was to determine whether the dynamic analysis of these components can help to predict tumour aggressiveness. METHODS AND RESULTS: An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs -1, -2, -7, -9, -11, -13 and -14 and TIMPs -1, -2 and -3. More than 5000 determinations on cancer specimens from 124 patients with invasive breast cancer were performed on the tumour centre core as well as on the invasive front. Immunostaining for MMPs/TIMPs on mononuclear inflammatory cells (MICs) was evaluated. To identify specific groups of tumours with distinct expression profiles, data obtained from both MICs populations were analysed by unsupervised hierarchical cluster analysis. When compared with MICs at the invasive front, intratumour MICs more frequently showed expression of MMP-7 and -1 and TIMP-3, but less frequently expression of MMP-9 and -11 and TIMP-2. CONCLUSIONS: Our data led us to consider the need of further studies in order to identify subsets of MICs and other protein elements of the microenvironment as attractive targets for new therapeutic strategies against cancer.
Subject(s)
Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Matrix Metalloproteinases/metabolism , Stromal Cells/metabolism , Tissue Inhibitor of Metalloproteinases/metabolism , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Chi-Square Distribution , Cluster Analysis , Female , Humans , Immunohistochemistry , Middle Aged , Prognosis , Stromal Cells/pathology , Tissue Array AnalysisABSTRACT
To assess whether breast arterial calcifications (BAC) are associated with altered serum markers of cardiovascular risk, mammograms and records from 1759 women (age range: 45-65 years) screened for breast cancer were revised. One hundred and forty seven (8.36%) women showed BAC. A total of 136 women with BAC and controls (mean age: 57 and 55 years, respectively) accepted entering the study. There were no significant differences in serum levels of urea, glucose, uric acid, creatinine, total cholesterol, HDL-C, LDL-C, folic acid, vitamin B(12), TSH or cysteine, between both groups of patients. However, women with BAC showed higher serum levels of triglycerides (p=0.006), homocysteine (p=0.002) and hs-CRP (p=0.003) than women without BAC. Likewise, we found a significantly higher percentage of cases with an elevated LDL-C/HDL-C ratio (coronary risk index >2) amongst women with BAC than in women without BAC (56.7 and 38.2%, respectively; p=0.04). Our results indicate that the finding of BAC identify women showing altered serum markers of cardiovascular risk.
