Portal de Periódicos da CAPES

The clinicopathological and prognostic significance of membrane type 1 matrix metalloproteinase (MT1‐MMP) and MMP‐9 according to their localization in invasive breast carcinoma

2007; Wiley; Volume: 50; Issue: 3 Linguagem: Inglês

10.1111/j.1365-2559.2007.02615.x

1365-2559

Eugenia Mylona, Alexandros Nomikos, Christina Μagkou, M Kamberou, Issidora S. Papassideri, Antonios Keramopoulos, L. Nakopoulou,

Peptidase Inhibition and Analysis

Aims: To investigate the clinicopathological and prognostic significance of membrane type 1 matrix metalloproteinase (MT1‐MMP) and MMP‐9 proteins expression in invasive breast carcinoma and their relationship to tumour proliferation and expression of c‐erbB2 and peroxisome proliferator‐activated receptor (PPAR) gamma. Methods: Immunohistochemistry was carried out on 175 paraffin‐embedded breast tissue specimens to detect MT1‐MMP, MMP‐9, oestrogen receptor (ER), progesterone receptor, c‐erbB‐2, Ki67, topoisomerase IIα (topo IIα) and PPARγ protein expression. Results: Both MT1‐MMP and MMP‐9 were expressed in the cytoplasm of the malignant cells and the peritumoral stroma. Cytoplasmic MT1‐MMP was more often observed in ER+ tumours ( P = 0.022), of a lower nuclear grade ( P = 0.020) and with reduced expression of Ki67 and topo IIα ( P = 0.027 and P = 0.006, respectively). Moreover, cytoplasmic MT1‐MMP was positively associated with MMP‐9 ( P = 0.010) and PPARγ ( P < 0.0001). Cytoplasmic MMP‐9 was inversely associated with Ki67 ( P = 0.034) and topo IIα ( P = 0.004), whereas its relationship with MT1‐MMP ( P = 0.034) and PPARγ ( P = 0.024) was found to be positive. Stromal MMP‐9 was more often observed in c‐erbB2+ tumours ( P = 0.043) and had an unfavourable impact on overall and relapse‐free survival in both univariate ( P = 0.0157 and P = 0.0274, respectively) and multivariate analyses ( P = 0.007 and P = 0.024, respectively). Conclusions: Cytoplasmic MT1‐MMP and MMP‐9 seem to be related to well‐differentiated tumours, with a low proliferation potential, while stromal MMP‐9 is associated with an aggressive tumour phenotype and is recognized as an independent poor prognostic indicator.