R F Araújo1, G A Lira2, J A Vilaça3, H G Guedes4, M C A Leitão4, H F Lucena5, C C O Ramos6. 1. Post Graduation Program in Functional and Structural Biology/Post Graduation Program Health Science/Department of Morphology, UFRN, Natal, RN, Brazil. Electronic address: araujojr@cb.ufrn.br. 2. Post Graduation Program Health Science, UFRN, Natal, RN, Brazil. 3. Medicine, Department of Morphology, UFRN, Natal, RN, Brazil. 4. Department of Morphology, UFRN, Natal, RN, Brazil. 5. Department of Oral Pathology, UFRN, Natal, RN, Brazil. 6. North Riograndense Association Against Cancer, Natal, RN, Brazil.
Abstract
PURPOSE: Angiogenesis and tumor invasion are complex processes that are mediated by various proteins, such as vascular endothelial growth factor (VEGF-α) and the matrix-degrading enzymes metalloproteinase-2 and -9 (MMP-2, MMP-9). The aim of this study was to determine what roles MMP-2, MMP-9, and VEGF-α play in colorectal cancer (CRC) by correlating their expression levels with the cancer TNM stage, modified Dukes criteria, degree of cell differentiation, and long-term patient survival. METHODS: The present series consisted of tissue samples obtained from 180 patients who had undergone large bowel resection during 1995 and 2005 at the Luis Antonio Hospital. Archival paraffin-embedded CRC tissue samples were used to generate tissue microarray blocks, which were immunohistochemically stained for MMP-2, MMP-9, and VEGF-α. Three different grading systems were applied to evaluate staining intensity. Chi-squared Person test and Kaplan-Meier survival curves were used, and values of p<0.05 were considered statistically significant. RESULTS: MMP-2 expression showed a significant association with more invasive cancer stages (p<0.001) and death (p<0.041). VEGF-α expression correlated with a high TNM stage (p<0.009), the degree of cell differentiation (p<0.025) and patient death as a result of disease (p<0.035). The Kaplan-Meier survival estimated that patients with strong staining for MMP-2 (log-rank x(2)=34.09; p<0.0001), MMP-9 (log-rank x(2)=12.83; p<0.0003) and VEGF (log-rank x(2)=33.9; p<0.0001) showed a greater tendency towards death during 60 months of follow up. CONCLUSIONS: The quantification of VEGF-α, MMP-2 and MMP-9 expression in colorectal cancer may be related to survival. These data add to the growing epidemiological and experimental evidence that VEGF-α, MMP-2 and MMP-9 may play a role in colorectal tumorigenesis.
PURPOSE: Angiogenesis and tumor invasion are complex processes that are mediated by various proteins, such as vascular endothelial growth factor (VEGF-α) and the matrix-degrading enzymes metalloproteinase-2 and -9 (MMP-2, MMP-9). The aim of this study was to determine what roles MMP-2, MMP-9, and VEGF-α play in colorectal cancer (CRC) by correlating their expression levels with the cancerTNM stage, modified Dukes criteria, degree of cell differentiation, and long-term patient survival. METHODS: The present series consisted of tissue samples obtained from 180 patients who had undergone large bowel resection during 1995 and 2005 at the Luis Antonio Hospital. Archival paraffin-embedded CRC tissue samples were used to generate tissue microarray blocks, which were immunohistochemically stained for MMP-2, MMP-9, and VEGF-α. Three different grading systems were applied to evaluate staining intensity. Chi-squared Person test and Kaplan-Meier survival curves were used, and values of p<0.05 were considered statistically significant. RESULTS:MMP-2 expression showed a significant association with more invasive cancer stages (p<0.001) and death (p<0.041). VEGF-α expression correlated with a high TNM stage (p<0.009), the degree of cell differentiation (p<0.025) and patientdeath as a result of disease (p<0.035). The Kaplan-Meier survival estimated that patients with strong staining for MMP-2 (log-rank x(2)=34.09; p<0.0001), MMP-9 (log-rank x(2)=12.83; p<0.0003) and VEGF (log-rank x(2)=33.9; p<0.0001) showed a greater tendency towards death during 60 months of follow up. CONCLUSIONS: The quantification of VEGF-α, MMP-2 and MMP-9 expression in colorectal cancer may be related to survival. These data add to the growing epidemiological and experimental evidence that VEGF-α, MMP-2 and MMP-9 may play a role in colorectal tumorigenesis.