Prognostic value of matrix metalloproteinases (MMP-2 and MMP-9) in patients with lymph node-negative breast carcinoma

Abstract

Twenty-five to thirty percent of patients with node-negative breast cancer are expected to relapse following surgery, therefore great efforts have been made to identify new prognostic markers that could be useful in defining patients for additional therapy. The expression of MMP-2 and MMP-9 has been associated with high potential of metastasis in several human carcinomas including breast cancer. In the present study we examined the prognostic value of immunoreactive MMP-2/MMP-9 protein in 270 consecutive lymph node negative cases who received radical mastectomy or modified radical mastectomy. Among the patients, 211 cases received adjuvant endocrine therapy and/or adjuvant chemotherapy. Using immunohistochemical assay, we found that 56.7% of the resected tumors were positive for MMP-2 whereas 59.6% of the samples were positive for MMP-9. Chi2 test demonstrated a significant direct association between MMP-2 and MMP-9 (p < 0.001); positive immunostaining of MMP-2 was significantly related to higher tumor grade (p < 0.001) and larger tumor size (p = 0.012); positive immunostaining of MMP-9 was significantly related to higher tumor grade (p = 0.002). In univariate analysis, using Cox-proportional hazard model we found MMP-2, MMP-9 and the co-expression of MMPs (MMP2/MMP9) were significantly associated with patients' relapse free survival (p = 0.016, 0.015 and 0.013 respectively) but not overall survival (p = 0.122, 0.320 and 0.091 respectively). Log-rank test also showed that MMP-2, MMP-9 or the co-expression of MMP2/MMP9 was unfavorable prognostic factor for relapse free survival but not overall survival. In subgroup analysis, we found MMPs were more prognostic for patients with no adjuvant treatment than for patients with adjuvant therapy. In multivariate analysis, using Cox-proportional hazard model we found co-expression of MMPs, larger tumor size and higher tumor grade were unfavorable for relapse free survival (p = 0.038, 0.007 and 0.015 for each). We concluded that MMP-2 and MMP-2 are unfavorable prognostic factors in breast cancer patients. They might be potential predictive factor for adjuvant systemic therapy. The co-expression of MMP-2 and MMP-9 has significantly prognostic value in node-negative patients.

Study of matrix metalloproteinases and their inhibitors in breast cancer

“…Our results are in accordance with those of previous reports showing that a high MMP-9 expression correlates significantly with tumoral aggressiveness and poor prognosis (Chantrain et al, 2004;Li et al, 2004;Pellikainen et al, 2004), as well as with other studies where high MMP-2 expression in carcinoma cells, in contrast, has been related to only a few inverse prognostic factors (Talvensaari-Mattila et al, 1998;Nakopoulou et al, 2003) or shown to have no association with clinicopathological parameters in breast cancer (Jones et al, 1999;Hirvonen et al, 2003;Talvensaari-Mattila et al, 2003). It has also been described that as breast cancer progresses, MMP-2 production increases during the early phases, whereas activation of MMP-9 occurs during the late cancerous stage (Liotta and Kohn, 2001), which could explain their different impact on prognosis in clinically detected invasive breast tumours.…”

Prognostic Value of Matrix Metalloproteinase 9 Expression in Breast Cancer Patients: A Meta-analysis

“…Furthermore, two studies (Pellikainen 2004;Gonzalez et al, 2010) provided information about MMP-9 expression in tumor cells and stromal tissues respectively without general result, which we treated independently. Eventually, 15 studies met the inclusion criteria were included (Scorilas et al, 2001;Fan et al, 2003;Li et al, 2004;Pellikainen et al, 2004;Rahko et al, 2004;Li et al, 2006;Mylona et al, 2007;Vizoso et al, 2007;Feng et al, 2008;Wu et al, 2008;Zhao et al, 2008;Tian et al, 2009;Gonzalez et al, 2010;Sullu et al, 2011;Oscar et al, 2012).…”

CITED2 is a novel direct effector of peroxisome proliferator‐activated receptor γ in suppressing hepatocellular carcinoma cell growth

“…[28][29][30] Taken together, the anti-HCC effect of CITED2 is in part mediated through upregulation of IFNA1, TNFRSF1A, TNFRSF25, CASP8, GZMA, and SERPINB5, and down-regulation of TERT and MMP2, which in turn suppresses HCC cell growth (Fig. 7).…”