146P - The prognostic value of MMP-9, MMP-2, TIMP-1 and TIMP-2 in breast cancer after twelve years of initial investigation

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Basic Science
Breast Cancer
Presenter DAN Jinga
Authors D.C. Jinga1, A. Blidaru2, I. Condrea3, C. Ardeleanu4, D. Median5, M. Stefanescu6, C. Matache6
  • 1Medical Oncology, UNIVERSITY BUCHAREST HOSPITAL, 050098 - BUCHAREST/RO
  • 2Surgical, "AL.TRESTIOREANU" NATIONAL INSTITUTE OF ONCOLOGY, BUCHAREST/RO
  • 3Pathology, "AL.TRESTIOREANU" NATIONAL INSTITUTE OF ONCOLOGY, BUCHAREST/RO
  • 4Pathology, VICTOR BABES NATIONAL INSTITUTE, bucharest/RO
  • 5Medical Oncology, Institute of Oncology Bucharest, Fundeni Clinical HospitalAlexandru Treistoreanu, RO-022328 - Bucharest/RO
  • 6Immunology, CANTACUZINO NATIONAL RESEARCH FOR MICROBIOLOGY AND IMMUNOLOGY, BUCHAREST/RO

Abstract

Background

The aim of this study was to investigate the prognostic power of matrixmetalloproteinases (MMP-9, MMP-2) expression and activity as well as their natural inhibitors (TIMP-1, TIMP-2) expression in breast cancer tumours.

Patients and methods

All of the experimental parameters were evaluated in fresh tumour tissue samples from thirty-two consecutive patients with primary invasive breast carcinomas collected between 2001-2002. Gelatinase activity (MMP-9 and MMP-2) was analysed by zymography while the expression level of MMP-9, MMP-2, TIMP-1 and TIMP-2 was quantified by commercial ELISA kits in 1% Triton-X 100 tumour extracts. The Mann-Whitney U test and Spearman's coefficient where calculated in order to establish the correlation of the experimentally determined parameters with relapse free survival (RFS), overall survival (OS) and the presence of metastasis and death (D) at the end of study.

Results

TIMP-1 expression was increased in the groups of patients with RSF < 104 months, with OS < 113 months and in those who died by comparison with their counterparts. These patients, especially the group with OS < 113 months, have also the lowest levels of TIMP-2 (p = 0.058). Therefore, MMP-2/TIMP-2 ratio distinguished statistically significant the groups of patients with OS greater and lower than 113 months (p = 0.051). On the other hand, TIMP-1/TIMP-2 ratio distinguished statistically significant groups of patients with RFS more than 104 months (p = 0.057), with OS more than 113 months (p = 0.068) or alive (p = 0.038) of their counterparts. TIMP-1/TIMP-2 ratio directly correlated with the death of patients (r = 0.381, p = 0.034), being significantly higher in the group of patients who died.

Conclusions

Our data suggested that as TIMP-1 expression is lower and TIMP-2 expression is higher, both relapse free survival and overall survival are higher. TIMP-1/TIMP-2 and MMP-2/TIMP-2 ratios seemed to be long term prognostic markers. These results are consistent with our previous observation that showed a direct correlation between MMP-2/TIMP-2 ratio and the value of Nottingham Prognostic Index.

Disclosure

All authors have declared no conflicts of interest.