Markers of progression and invasion in short term follow up of untreated breast cancer patients

Cancer Biomark. 2015;15(6):745-54. doi: 10.3233/CBM-150516.

Abstract

Background: Cancer progression and metastasis are complex processes, dependent of molecules involved in inflammation, degradation and invasion. These molecules can be used as prognostic indicators to single out patients with higher risk of recurrence. Interleukin-8 (IL-8) has a role in inflammation, urokinase plasminogen activator (uPA), plasminogen activator inhibitor type-1 (PAI-1) and matrix metalloproteinase-2, -9 have a decisive part in the process of degradation and invasion, while vascular endothelial growth factor (VEGF) is consequential for angiogenesis.

Objectives: Aim of our study is to determine relations between IL-8, uPA, PAI-1, MMP-2, -9, VEGF as their prognostic significance in terms of recurrence free survival.

Methods: This study included 91 untreated patients with lymph node negative (N0) primary breast cancer.

Results: Patients with higher levels of uPA (p= 0.05), PAI-1 (0.05), MMP2 (p= 0.05) and IL-8 (p= 0.02) have a poor prognosis. Positive correlations were found between ER - PR, uPA - PAI-1, uPA - MMP9, PAI-1 - IL-8, MMP9 - IL-8, MMP9 - VEGF. Negative correlations were found between ER - IL-8, uPA - IL-8, MMP2 - VEGF.

Conclusions: Higher concentrations of IL-8, uPA, PAI-1 and MMP2, as is MMP9 and VEGF, confirmed aggressive phenotype and poor prognosis in different subgroups.

Keywords: Breast cancer; interleukin 8; lymph node; matrix metalloproteinase; plasminogen activator; prognostic markers; progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / surgery
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / secondary*
  • Carcinoma, Ductal, Breast / surgery
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / secondary*
  • Carcinoma, Lobular / surgery
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Interleukin-8 / metabolism
  • Lymphatic Metastasis
  • Mastectomy
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasm Recurrence, Local / surgery
  • Neoplasm Staging
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Survival Rate
  • Urokinase-Type Plasminogen Activator / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Biomarkers, Tumor
  • Interleukin-8
  • Plasminogen Activator Inhibitor 1
  • Receptors, Estrogen
  • Receptors, Progesterone
  • SERPINE1 protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Urokinase-Type Plasminogen Activator
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9