A comparative study of protein expression in primary colorectal cancer and synchronous hepatic metastases: The significance of matrix metalloproteinase-1 expression as a predictor of liver metastasis

Young Wan Kim, Yong Taek Ko, Nam Kyu Kim, Hyun Cheol Chung, Byung Soh Min, Kang Young Lee, Jong Pil Park, Hoguen Kim

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Abstract

Objective. This study was undertaken to determine the ability of protein expression in primary colorectal cancer and metastatic liver tumour tissues to predict hepatic metastasis and intrahepatic recurrence. Material and methods. Sixty patients with colorectal cancer were enrolled in this study. The expression of the following five proteins was assessed by immunohistochemical (IHC) staining: carcinoembryonic antigen (CEA); vascular endothelial growth factor (VEGF); matrix metalloproteinase (MMP)-1; MMP-7; and tissue inhibitor of metalloproteinases (TIMP)-1. Protein expression was measured in patients with primary colorectal cancer without liver metastasis (Group A), in patients with primary colorectal cancer with liver metastasis (primary tumour; Group B), and in patients with resected metastatic liver tumour tissues (liver metastasis; Group C). Results. IHC staining revealed more protease activity (MMP-1 and -7) in Group B than in Group A. Angiogenic activity (positive VEGF expression) was significantly greater in Group C than in Group B. Multivariate analysis showed that positive MMP-1 expression, the presence of lymphovascular invasion, and an elevated pre-operative serum CEA level (> 5 ng/ml) were significantly related to synchronous liver metastasis. However, intrahepatic recurrence was not related to protein expression, the presence of lymphovascular invasion, or the pre-operative CEA level. Conclusions. Our findings suggest that protease activity is important for metastasis, and that angiogenic activity is essential for metastatic tumour growth. Furthermore, positive MMP-1 expression in primary colorectal tumour tissues was a significant predictor of liver metastasis. However, the prognostic impact of protein marker expression in terms of intrahepatic recurrence appears to be minimal.

Original languageEnglish
Pages (from-to)217-225
Number of pages9
JournalScandinavian Journal of Gastroenterology
Volume45
Issue number2
DOIs
Publication statusPublished - 2010 Feb 22

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Matrix Metalloproteinase 1
Colorectal Neoplasms
Neoplasm Metastasis
Liver
Carcinoembryonic Antigen
Liver Neoplasms
Matrix Metalloproteinase 7
Proteins
Recurrence
Vascular Endothelial Growth Factor A
Neoplasms
Peptide Hydrolases
Staining and Labeling
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase Inhibitors
Multivariate Analysis
Growth
Serum

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

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title = "A comparative study of protein expression in primary colorectal cancer and synchronous hepatic metastases: The significance of matrix metalloproteinase-1 expression as a predictor of liver metastasis",
abstract = "Objective. This study was undertaken to determine the ability of protein expression in primary colorectal cancer and metastatic liver tumour tissues to predict hepatic metastasis and intrahepatic recurrence. Material and methods. Sixty patients with colorectal cancer were enrolled in this study. The expression of the following five proteins was assessed by immunohistochemical (IHC) staining: carcinoembryonic antigen (CEA); vascular endothelial growth factor (VEGF); matrix metalloproteinase (MMP)-1; MMP-7; and tissue inhibitor of metalloproteinases (TIMP)-1. Protein expression was measured in patients with primary colorectal cancer without liver metastasis (Group A), in patients with primary colorectal cancer with liver metastasis (primary tumour; Group B), and in patients with resected metastatic liver tumour tissues (liver metastasis; Group C). Results. IHC staining revealed more protease activity (MMP-1 and -7) in Group B than in Group A. Angiogenic activity (positive VEGF expression) was significantly greater in Group C than in Group B. Multivariate analysis showed that positive MMP-1 expression, the presence of lymphovascular invasion, and an elevated pre-operative serum CEA level (> 5 ng/ml) were significantly related to synchronous liver metastasis. However, intrahepatic recurrence was not related to protein expression, the presence of lymphovascular invasion, or the pre-operative CEA level. Conclusions. Our findings suggest that protease activity is important for metastasis, and that angiogenic activity is essential for metastatic tumour growth. Furthermore, positive MMP-1 expression in primary colorectal tumour tissues was a significant predictor of liver metastasis. However, the prognostic impact of protein marker expression in terms of intrahepatic recurrence appears to be minimal.",
author = "Kim, {Young Wan} and Ko, {Yong Taek} and Kim, {Nam Kyu} and Chung, {Hyun Cheol} and Min, {Byung Soh} and Lee, {Kang Young} and Park, {Jong Pil} and Hoguen Kim",
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T1 - A comparative study of protein expression in primary colorectal cancer and synchronous hepatic metastases

T2 - The significance of matrix metalloproteinase-1 expression as a predictor of liver metastasis

AU - Kim, Young Wan

AU - Ko, Yong Taek

AU - Kim, Nam Kyu

AU - Chung, Hyun Cheol

AU - Min, Byung Soh

AU - Lee, Kang Young

AU - Park, Jong Pil

AU - Kim, Hoguen

PY - 2010/2/22

Y1 - 2010/2/22

N2 - Objective. This study was undertaken to determine the ability of protein expression in primary colorectal cancer and metastatic liver tumour tissues to predict hepatic metastasis and intrahepatic recurrence. Material and methods. Sixty patients with colorectal cancer were enrolled in this study. The expression of the following five proteins was assessed by immunohistochemical (IHC) staining: carcinoembryonic antigen (CEA); vascular endothelial growth factor (VEGF); matrix metalloproteinase (MMP)-1; MMP-7; and tissue inhibitor of metalloproteinases (TIMP)-1. Protein expression was measured in patients with primary colorectal cancer without liver metastasis (Group A), in patients with primary colorectal cancer with liver metastasis (primary tumour; Group B), and in patients with resected metastatic liver tumour tissues (liver metastasis; Group C). Results. IHC staining revealed more protease activity (MMP-1 and -7) in Group B than in Group A. Angiogenic activity (positive VEGF expression) was significantly greater in Group C than in Group B. Multivariate analysis showed that positive MMP-1 expression, the presence of lymphovascular invasion, and an elevated pre-operative serum CEA level (> 5 ng/ml) were significantly related to synchronous liver metastasis. However, intrahepatic recurrence was not related to protein expression, the presence of lymphovascular invasion, or the pre-operative CEA level. Conclusions. Our findings suggest that protease activity is important for metastasis, and that angiogenic activity is essential for metastatic tumour growth. Furthermore, positive MMP-1 expression in primary colorectal tumour tissues was a significant predictor of liver metastasis. However, the prognostic impact of protein marker expression in terms of intrahepatic recurrence appears to be minimal.

AB - Objective. This study was undertaken to determine the ability of protein expression in primary colorectal cancer and metastatic liver tumour tissues to predict hepatic metastasis and intrahepatic recurrence. Material and methods. Sixty patients with colorectal cancer were enrolled in this study. The expression of the following five proteins was assessed by immunohistochemical (IHC) staining: carcinoembryonic antigen (CEA); vascular endothelial growth factor (VEGF); matrix metalloproteinase (MMP)-1; MMP-7; and tissue inhibitor of metalloproteinases (TIMP)-1. Protein expression was measured in patients with primary colorectal cancer without liver metastasis (Group A), in patients with primary colorectal cancer with liver metastasis (primary tumour; Group B), and in patients with resected metastatic liver tumour tissues (liver metastasis; Group C). Results. IHC staining revealed more protease activity (MMP-1 and -7) in Group B than in Group A. Angiogenic activity (positive VEGF expression) was significantly greater in Group C than in Group B. Multivariate analysis showed that positive MMP-1 expression, the presence of lymphovascular invasion, and an elevated pre-operative serum CEA level (> 5 ng/ml) were significantly related to synchronous liver metastasis. However, intrahepatic recurrence was not related to protein expression, the presence of lymphovascular invasion, or the pre-operative CEA level. Conclusions. Our findings suggest that protease activity is important for metastasis, and that angiogenic activity is essential for metastatic tumour growth. Furthermore, positive MMP-1 expression in primary colorectal tumour tissues was a significant predictor of liver metastasis. However, the prognostic impact of protein marker expression in terms of intrahepatic recurrence appears to be minimal.

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