title: The prognostic role of interleukin-8 (IL-8) and matrix metalloproteinases -2 and -9 in lymph node-negative untreated breast cancer patients.
abstract: OBJECTIVE
  To investigate the relationships, if any, between interleukin (IL) -8/matrix metalloproteinase (MMP)-2/ MMP-9 and other prognostic variables in lymph node-negative untreated breast cancer patients, and to determine the prognostic value of these potential biomarkers.
  
  
  METHODS
  The study included 135 patients with known clinicopathological parameters. IL-8, MMP-2 and MMP-9 levels were determined by ELISA in primary tumor tissue lysates.
  
  
  RESULTS
  There were no significant relationships between IL-8/MMP-2/MMP-9 expression and available clinicopathological parameters (patient age, menopausal status, tumor size and tumor grade). Estrogen receptor (ER)- patients had higher levels of both IL-8 and MMP-9 (p=0.006 and p=0.04, respectively) compared to ER+ patients; there was a significant negative correlation between ER and IL-8 (p=0.02). MMP-9 expression was significantly higher in patients with higher levels of IL-8 (p<0.001) and there was a significant positive correlation between IL-8 and MMP-9, as well as between progesterone receptor (PR) and MMP-2 (p<0.001 and p=0.05, respectively). PR+ patients had higher levels of MMP-2 than PR- patients (p=0.03). Among the investigated biomarkers, only IL-8 had a statistically significant prognostic value in terms of relapse free survival (RFS) (p<0.001). Patients with higher levels of IL-8 had worse prognosis.
  
  
  CONCLUSIONS
  Expression of IL-8 and consequently expression of MMP-9 could be hormonally regulated in breast cancer. IL-8 could be a marker of more aggressive, ER- breast cancer phenotype. Different expression of MMP-2 and MMP-9 regarding differential hormonal receptor expression could indicate distinct mechanisms of their regulation. It seems that IL-8 is a strong and independent unfavorable prognostic parameter in node-negative breast cancer. Node-negative patients with higher levels of IL-8 should be treated with adjuvant, especially IL-8 targeted therapy.
authors.affiliation: Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, Belgrade, Serbia.
authors.forename: J
authors.initials: J
authors.lastname: Milovanovic
authors.forename: N
authors.initials: N
authors.lastname: Todorovic-Rakovic
authors.forename: Z
authors.initials: Z
authors.lastname: Abu Rabi
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis*; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D008875:Middle Aged; D060787:Neoplasm Grading; D011237:Predictive Value of Tests; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; C508606:CXCL8 protein, human; D016209:Interleukin-8; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9