Potential clinical relevance of uPA and PAI-1 levels in node-negative, postmenopausal breast cancer patients bearing histological grade II tumors with ER/PR expression, during an early follow-up

Tumour Biol. 2015 Sep;36(10):8193-200. doi: 10.1007/s13277-015-3573-1. Epub 2015 May 21.

Abstract

We evaluated urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) prognostic value in postmenopausal, node-negative breast cancer patients bearing tumors with estrogen receptor (ER)/progesterone receptor (PR) expression, treated with locoregional therapy alone, within an early follow-up. We focused our analysis on tumors of histological grade II in order to improve its prognostic value and, consequently, to improve a decision-making process. The cytosol extracts of 73 tumor samples were used for assessing several biomarkers. ER and PR levels were measured by classical biochemical method. Cathepsin D was assayed by a radiometric immunoassay while both uPA and PAI-1 level determinations were performed by enzyme-linked immunosorbent assays. HER-2 gene amplification was determined by chromogenic in situ hybridization (CISH) in primary tumor tissue. Patients bearing tumors smaller than or equal to 2 cm (pT1) or those with low PAI-1 levels (PAI-1 < 6.35 pg/mg) showed favorable outcome compared to patients bearing tumors greater than 2 cm (pT2,3) or those with high PAI-1 levels, respectively. Analyses of 4 phenotypes, defined by tumor size and PAI-1 status, revealed that patients bearing either pT1 tumors, irrespective of PAI-1 levels, or pT2,3 tumors with low PAI-1 levels, had similar disease-free interval probabilities and showed favorable outcome compared to those bearing pT2,3 tumors with high PAI-1 levels. Our findings suggest that tumor size and PAI-1, used in combination as phenotypes are not only prognostic but might also be predictive in node-negative, postmenopausal breast cancer patients bearing histological grade II tumors with ER/PR expression, during an early follow-up period.

Keywords: Biomarkers; Early follow-up; Locoregional therapy; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / pathology*
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / mortality
  • Carcinoma, Lobular / pathology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization, Fluorescence
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Plasminogen Activator Inhibitor 1 / metabolism*
  • Postmenopause
  • Prognosis
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism*
  • Retrospective Studies
  • Survival Rate
  • Urokinase-Type Plasminogen Activator / metabolism*

Substances

  • Biomarkers, Tumor
  • Plasminogen Activator Inhibitor 1
  • Receptors, Estrogen
  • Receptors, Progesterone
  • SERPINE1 protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Urokinase-Type Plasminogen Activator