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Matrix metalloproteinase-2 (MMP-2) is associated with survival in breast carcinoma.

ABSTRACT: Adjuvant therapy is one of the major advances in the treatment of breast carcinoma patients - but do all patients need it? New predictive markers, which are able to save breast carcinoma patients from the most toxic adjuvant therapies, are still needed. The expression of matrix metalloproteinases (MMP-2) has been previously linked to invasiveness of carcinoma cells. In this study, we explored the role of MMP-2 as a prognostic factor in breast carcinoma in a large series to be able to show the favourable effect of MMP-2 negativity in poor prognosis subgroup of hormone receptor-negative patients. The MMP-2 immunoreactive protein was evaluated from primary adenocarcinoma of the breast in 453 cases by using a specific monoclonal antibody in immunohistochemical stainings. The MMP-2 protein found in breast carcinoma tumour cells was here shown to be associated with a shortened recurrence-free survival or relative overall survival (P=0.03). It was shown here that MMP-2 negativity is significantly linked to favourable prognosis in patients considered to be at risk due to their hormone receptor negativity. In the patient group presenting with a progesterone receptor-negative tumour, the survival rate of the MMP-2-positive cases was 58% while it was 95% in MMP-2-negative cases after 10 years of follow-up (P=0.005). The present data shows for the first time that MMP-2 negativity could serve as a marker for favourable prognosis in breast carcinoma patients with a hormone receptor-negative tumour usually associated with high risk. MMP-2 is also shown to correlate to shortened survival independent of major prognostic indicators in patients with primary breast carcinoma.

SUBMITTER: Talvensaari-Mattila A

PROVIDER: S-EPMC2394290 | biostudies-other | 2003 Oct

REPOSITORIES: biostudies-other

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Project description:BACKGROUND:The role of tumor-associated macrophages (TAMs) in the cancer immune landscape and their potential as treatment targets or modulators of response to treatment are gaining increasing interest. TAMs display high molecular and functional complexity. Therefore their objective assessment as breast cancer biomarkers is critical. The aims of this study were to objectively determine the in situ expression and significance of TAM biomarkers (CD68, CD163, and MMP-9) in breast cancer and to identify subclasses of patients who could benefit from TAM-targeting therapies. METHODS:We measured CD68, CD163, and MMP-9 protein expression in formalin-fixed paraffin-embedded tissues of breast carcinomas represented in tissue microarray format using multiplexed quantitative immunofluorescence (QIF) in two independent Yale cohorts: cohort A-n = 398, estrogen receptor-positive (ER+) and ER- cases-and the triple-negative breast cancer (TNBC)-only cohort B (n = 160). Associations between macrophage markers, ER status, and survival were assessed. Protein expression measured by QIF was compared with mRNA expression data from the METABRIC study. RESULTS:All three macrophage markers were co-expressed, displaying higher expression in ER- cancers. High pan-macrophage marker CD68 correlated with poorer overall survival (OS) only in ER- cases of cohort A (P = 0.02). High expression of CD163 protein in TAMs was associated with improved OS in ER- cases (cohort A, P = 0.03 and TNBC cohort B, P = 0.04, respectively) but not in ER+ cancers. MMP-9 protein was not individually associated with OS. High expression of MMP-9 in the CD68+/CD163+ TAMs was associated with worse OS in ER+ tumors (P <0.001) but not in ER- cancers. In the METABRIC dataset, mRNA levels followed the co-expression pattern observed in QIF but did not always show the same trend regarding OS. CONCLUSIONS:Macrophage activity markers correlate with survival differently in ER+ and ER- cancers. The association between high co-expression and co-localization of MMP-9/CD163/CD68 and poor survival in ER+ cancers suggests that these cancers may be candidates for macrophage-targeted therapies.

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Matrix metalloproteinase-2 (MMP-2) is associated with survival in breast carcinoma.

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