Matrix metalloproteinase 13 activity is associated with poor prognosis in colorectal cancer

M. F. Leeman, J. A. McKay, Graeme Ian Murray

Research output: Contribution to journalArticle

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Abstract

Aims: The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes collectively capable of degrading all extracellular matrix components, in particular fibrillar collagen. The importance of this group of proteins in the processes of tumour invasion and metastasis is now widely acknowledged. MMP-13 (collagenase 3) has a central role in the MMP activation cascade. The purpose of this study was to investigate the presence and activity of MMP-13 in colorectal cancer and relate these to clinicopathological features.

Methods: Immunohistochemistry for MMP-1 3 was performed on formalin fixed, paraffin wax embedded sections of a large series of colorectal cancers (n = 249), all of which had uniform clinical and pathological information available. Immunoreactivity to MMP-13 was detected with a monoclonal antibody to MMP-13 using a Dako TechMate(TM)500 automated immunostaining system. The presence and cellular localisation of MMP-13 was assessed using a semiquantitative scoring system. Gelatin zymography was used to detect and measure MMP-13 activity. The zymography was performed on a subset of the cases studied by immunohistochemistry using two groups of 10 paired Dukes's C turnouts and normal samples, selected by either having "good" or "poor" survival.

Results: Immunoreactivity to MMP-13 was identified in 91% of cases and immunoreactivity was localised to the cytoplasm of tumour cells. A high MMP-13 staining score showed a trend towards poorer survival. Tumours had significantly greater MMP-13 activity compared with normal colonic mucosa (p < 0.001). Furthermore, the turnout to normal tissue ratio was significantly higher in the poor survival group (p = 0.02).

Conclusions: These results show that MMP-13 is frequently present and active in colorectal cancer and suggest that the activity of MMP-13 is associated with poorer survival in colorectal cancer.

Original languageEnglish
Pages (from-to)758-762
Number of pages4
JournalJournal of Clinical Pathology
Volume55
Issue number10
DOIs
Publication statusPublished - 2002

Keywords

  • SQUAMOUS-CELL CARCINOMAS
  • COLLAGENASE-3 MMP-13
  • TUMOR INVASION
  • GELATINASE-A
  • EXPRESSION
  • ACTIVATION
  • METASTASIS
  • MT1-MMP
  • MARKERS

Cite this

Matrix metalloproteinase 13 activity is associated with poor prognosis in colorectal cancer. / Leeman, M. F.; McKay, J. A.; Murray, Graeme Ian.

In: Journal of Clinical Pathology, Vol. 55, No. 10, 2002, p. 758-762.

Research output: Contribution to journalArticle

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abstract = "Aims: The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes collectively capable of degrading all extracellular matrix components, in particular fibrillar collagen. The importance of this group of proteins in the processes of tumour invasion and metastasis is now widely acknowledged. MMP-13 (collagenase 3) has a central role in the MMP activation cascade. The purpose of this study was to investigate the presence and activity of MMP-13 in colorectal cancer and relate these to clinicopathological features.Methods: Immunohistochemistry for MMP-1 3 was performed on formalin fixed, paraffin wax embedded sections of a large series of colorectal cancers (n = 249), all of which had uniform clinical and pathological information available. Immunoreactivity to MMP-13 was detected with a monoclonal antibody to MMP-13 using a Dako TechMate(TM)500 automated immunostaining system. The presence and cellular localisation of MMP-13 was assessed using a semiquantitative scoring system. Gelatin zymography was used to detect and measure MMP-13 activity. The zymography was performed on a subset of the cases studied by immunohistochemistry using two groups of 10 paired Dukes's C turnouts and normal samples, selected by either having {"}good{"} or {"}poor{"} survival.Results: Immunoreactivity to MMP-13 was identified in 91{\%} of cases and immunoreactivity was localised to the cytoplasm of tumour cells. A high MMP-13 staining score showed a trend towards poorer survival. Tumours had significantly greater MMP-13 activity compared with normal colonic mucosa (p < 0.001). Furthermore, the turnout to normal tissue ratio was significantly higher in the poor survival group (p = 0.02).Conclusions: These results show that MMP-13 is frequently present and active in colorectal cancer and suggest that the activity of MMP-13 is associated with poorer survival in colorectal cancer.",
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TY - JOUR

T1 - Matrix metalloproteinase 13 activity is associated with poor prognosis in colorectal cancer

AU - Leeman, M. F.

AU - McKay, J. A.

AU - Murray, Graeme Ian

PY - 2002

Y1 - 2002

N2 - Aims: The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes collectively capable of degrading all extracellular matrix components, in particular fibrillar collagen. The importance of this group of proteins in the processes of tumour invasion and metastasis is now widely acknowledged. MMP-13 (collagenase 3) has a central role in the MMP activation cascade. The purpose of this study was to investigate the presence and activity of MMP-13 in colorectal cancer and relate these to clinicopathological features.Methods: Immunohistochemistry for MMP-1 3 was performed on formalin fixed, paraffin wax embedded sections of a large series of colorectal cancers (n = 249), all of which had uniform clinical and pathological information available. Immunoreactivity to MMP-13 was detected with a monoclonal antibody to MMP-13 using a Dako TechMate(TM)500 automated immunostaining system. The presence and cellular localisation of MMP-13 was assessed using a semiquantitative scoring system. Gelatin zymography was used to detect and measure MMP-13 activity. The zymography was performed on a subset of the cases studied by immunohistochemistry using two groups of 10 paired Dukes's C turnouts and normal samples, selected by either having "good" or "poor" survival.Results: Immunoreactivity to MMP-13 was identified in 91% of cases and immunoreactivity was localised to the cytoplasm of tumour cells. A high MMP-13 staining score showed a trend towards poorer survival. Tumours had significantly greater MMP-13 activity compared with normal colonic mucosa (p < 0.001). Furthermore, the turnout to normal tissue ratio was significantly higher in the poor survival group (p = 0.02).Conclusions: These results show that MMP-13 is frequently present and active in colorectal cancer and suggest that the activity of MMP-13 is associated with poorer survival in colorectal cancer.

AB - Aims: The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes collectively capable of degrading all extracellular matrix components, in particular fibrillar collagen. The importance of this group of proteins in the processes of tumour invasion and metastasis is now widely acknowledged. MMP-13 (collagenase 3) has a central role in the MMP activation cascade. The purpose of this study was to investigate the presence and activity of MMP-13 in colorectal cancer and relate these to clinicopathological features.Methods: Immunohistochemistry for MMP-1 3 was performed on formalin fixed, paraffin wax embedded sections of a large series of colorectal cancers (n = 249), all of which had uniform clinical and pathological information available. Immunoreactivity to MMP-13 was detected with a monoclonal antibody to MMP-13 using a Dako TechMate(TM)500 automated immunostaining system. The presence and cellular localisation of MMP-13 was assessed using a semiquantitative scoring system. Gelatin zymography was used to detect and measure MMP-13 activity. The zymography was performed on a subset of the cases studied by immunohistochemistry using two groups of 10 paired Dukes's C turnouts and normal samples, selected by either having "good" or "poor" survival.Results: Immunoreactivity to MMP-13 was identified in 91% of cases and immunoreactivity was localised to the cytoplasm of tumour cells. A high MMP-13 staining score showed a trend towards poorer survival. Tumours had significantly greater MMP-13 activity compared with normal colonic mucosa (p < 0.001). Furthermore, the turnout to normal tissue ratio was significantly higher in the poor survival group (p = 0.02).Conclusions: These results show that MMP-13 is frequently present and active in colorectal cancer and suggest that the activity of MMP-13 is associated with poorer survival in colorectal cancer.

KW - SQUAMOUS-CELL CARCINOMAS

KW - COLLAGENASE-3 MMP-13

KW - TUMOR INVASION

KW - GELATINASE-A

KW - EXPRESSION

KW - ACTIVATION

KW - METASTASIS

KW - MT1-MMP

KW - MARKERS

U2 - 10.1136/jcp.55.10.758

DO - 10.1136/jcp.55.10.758

M3 - Article

VL - 55

SP - 758

EP - 762

JO - Journal of Clinical Pathology

JF - Journal of Clinical Pathology

SN - 0021-9746

IS - 10

ER -