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MMP-2 Protein in Invasive Breast Cancer and the Impact of MMP-2/TIMP-2 Phenotype on Overall Survival

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Abstract

Crucial event in the metastasis of cancer cells is the secretion of matrix metalloproteinases (MMPs), which are responsible for the degradation of extracellular matrix (ECM). Among them, matrix metalloproteinase-2 (MMP-2) is a gelatinase, which degrades basement membrane type-IV collagen. Immunohistochemistry was performed to detect MMP-2 protein in 135 infiltrative breast carcinomas. MMP-2 was studied along with clinicopathological parameters (tumor size, histological type, nuclear and histological grade, stage, lymph node status, ER, and PR), patients' survival and tissue inhibitor metalloproteinase-2 (TIMP-2), Ki-67, and p53 proteins. MMP-2 immunoreactivity was detected in the cytoplasm in cancer cells in 102 (75.6%) and in both tumor and tumor stromal cells in 37 (27.4%) of 135 cases respectively. MMP-2 reactivity in cancer cells displayed a statistically significant association with tumor size > 2 cm (p = 0.022). In tumor stromal cells a strong parallel association was observed between the expression of MMP-2 and TIMP-2 (p = 0.015), while an inverse correlation was found between MMP-2 and both Ki-67 and p53 (p = 0.033 and p = 0.034 respectively). In the subgroup with negative lymph nodes MMP-2 was also inversely associated with p53 in cancer cells (p = 0.045). Finally a statistically significant association was revealed using Kaplan–Meier and Cox's proportional hazard regression model between the MMP-2/TIMP-2 phenotype and patients' better survival (p = 0.021). Our results point out the strong relation between MMP-2 and TIMP-2 and the effect of the MMP-2/TIMP-2 phenotype in the patients' overall survival. The inverse correlation between MMP-2 and both Ki-67 and p53 can be explained by the potential inhibition of MMP-2 by TIMP-2. These results suggest the necessity of further investigation.

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Authors and Affiliations

  1. Department of Pathology, Medical School, The National and Kapodistrian University of Athens, Greece

    Lydia Nakopoulou, Ioanna Tsirmpa, Paraskevi Alexandrou & Panayiotis S. Davaris

  2. Department of Gynaecology and Obstetrics, Medical School, The National and Kapodistrian University of Athens, Greece

    Androniki Louvrou & Constantine Ampela

  3. Department of Pathology, Alexandra's Hospital, Athens, Greece

    Sophia Markaki

Authors
  1. Lydia Nakopoulou
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  2. Ioanna Tsirmpa
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Nakopoulou, L., Tsirmpa, I., Alexandrou, P. et al. MMP-2 Protein in Invasive Breast Cancer and the Impact of MMP-2/TIMP-2 Phenotype on Overall Survival. Breast Cancer Res Treat 77, 145–155 (2003). https://doi.org/10.1023/A:1021371028777

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