Expression of matrix metalloproteinases and their inhibitors in medulloblastomas and their prognostic relevance.

Abstract

PURPOSE AND EXPERIMENTAL DESIGN:

The cellular mechanisms leading to metastatic disease in medulloblastoma (MB), the most common malignant brain tumor in childhood, are mainly unknown. Recently, however, the involvement of matrix metalloproteinases (MMPs) has been suggested. We examined the expression and localization of four MMPs-MMP-2 and -9, membrane-type 1 and 2 MMP (MT1- and MT2-MMP)-and correlated the data with those for their main inhibitors, tissue inhibitors of metalloproteinases (TIMP-1, -2, and -3), in 83 classical and 18 desmoplastic MBs.

RESULTS:

Independent of the histological subtype, MMP-2 expression was found in a small percentage of tumors, whereas MMP-9 and MT1- or MT2-MMP were expressed in >75% of tumor samples. The expression of TIMP-1, -2, and -3, on the other hand, was found to depend on the histological subtype: TIMP-3 was often found in classical MB, whereas TIMP-2 was often expressed in desmoplastic MB (P = 0.007-0.001). In addition, both TIMP-3 and -2 correlated significantly with the expression of all studied metalloproteinases except MMP-2. TIMP-1, detected only in classical MB in a low percentage, was the only TIMP that correlated with the expression of MMP-2. Kaplan-Meier estimation revealed significantly reduced long-term survival of patients with strong MMP expression in tumor samples. In multivariate logistic regression analysis, however, the prognosis was significantly determined only by clinical parameters.

CONCLUSIONS:

TIMP-3 and -2 expression is highly correlated with histological subtypes of MBs and strongly associated with the expression of certain MMPs. The expression of TIMPs and MMPs, however, does not determine prognosis independently of clinical parameters.

• Authors: Ozlem Ozen, Bjarne Krebs, Bernhard Hemmerlein, Arnulf Pekrun, Hans Kretzschmar, Jochen Herms
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 10 Issue 14 Pg. 4746-53 (Jul 15 2004) ISSN: 1078-0432 [Print] United States
• PMID: 15269148 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MMP15 protein, human
• Tissue Inhibitor of Metalloproteinase-1
• Tissue Inhibitor of Metalloproteinase-3
• Tissue Inhibitor of Metalloproteinases
• Tissue Inhibitor of Metalloproteinase-2
• Matrix Metalloproteinase 15
• Matrix Metalloproteinases
• Matrix Metalloproteinases, Membrane-Associated
• Metalloendopeptidases
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Adolescent
• Adult
• Child
• Child, Preschool
• Female
• Humans
• Immunohistochemistry
• Infant
• Logistic Models
• Male
• Matrix Metalloproteinase 15
• Matrix Metalloproteinase 2 (biosynthesis)
• Matrix Metalloproteinase 9 (biosynthesis)
• Matrix Metalloproteinases (biosynthesis)
• Matrix Metalloproteinases, Membrane-Associated
• Medulloblastoma (metabolism, pathology)
• Metalloendopeptidases (biosynthesis)
• Middle Aged
• Multivariate Analysis
• Prognosis
• Survival Analysis
• Tissue Inhibitor of Metalloproteinase-1 (biosynthesis)
• Tissue Inhibitor of Metalloproteinase-2 (biosynthesis)
• Tissue Inhibitor of Metalloproteinase-3 (biosynthesis)
• Tissue Inhibitor of Metalloproteinases (biosynthesis)