Correlation between the immunohistochemical expressions of MMP-1, MMP-7 and VEGF and prognostic factors in colorectal adenocarcinoma

Abstract

PURPOSE: To analyze the expression of metalloproteinase-1, metalloproteinase-7 and vascular endothelial growth factor (VEGF) in colorectal adenocarcinoma, and to correlate these with the clinical-pathological prognostic factors. METHODS: Tumor tissue from 82 patients was fixed in formalin and embedded in paraffin blocks. These samples were analyzed by means of the streptavidin-biotin immunohistochemical method, using the tissue microarray technique. Marker positivity was evaluated using categorical scores that determined cutoff percentages of stained tumor cells. Protein tissue expression was correlated with the variables of degree of cell differentiation, staging, disease-free interval, recurrence, survival and specific mortality. The Fisher exact and Kaplan-Meier tests were used to assess associations between the markers and the study variables. The log-rank and Wilcoxon tests were used to assess the significance of differences between curves of disease-free interval and survival. RESULTS: All tumors were positive for metalloproteinase-1; 50 (61%) were positive and 32 (39%) were negative for metalloproteinase-7; and 60 (74.1%) were positive and 21 (25.9%) were negative for VEGF. Correlation of marker expression, both in groups and individually, did not show statistical significance in relation to the degree of cell differentiation, staging, disease-free interval, survival or specific mortality. Recurrence showed a statistically significant correlation with positive expression of the three markers, when analyzed as a group (p = 0.038). CONCLUSION: The associated expression of metalloproteinase-1, metalloproteinase-7 and VEGF in colorectal adenocarcinoma is related to the incidence of disease recurrence.

Immunohistochemical expression of MMP-7 protein and its serum level in colorectal cancer

“…The current study confirmed the observations of other authors that MMP-7 expression in colorectal cancer tissues is markedly higher than in normal intestinal mucosa, which proves the involvement of this metalloproteinase in CRC growth [26][27][28][29][30]. Also the finding of enhanced MMP-7 mRNA confirmed the involvement [11,31,32].…”

“…The statistical analysis showed only a stronger relationship of MMP-7 overexpression with tumours located in the colon as compared to those in the rectum. However, we revealed no significant correlations between MMP-7 expression in tumour cells and CRC advancement, similarly to Gomes et al [26], who used antibody that detected both pro-and active forms of MMP-7. However, investigations done by Wang et al [33] proved the correlation of positive MMP-7 expression with tumour infiltration depth in the intestinal wall and with distant metastases.…”

Expressions of TIMP-1, COX-2 and MMP-7 in Colon Polyp and Colon Cancer

“…While Luo et al found that in cancer patients MMP-7 expression was correlated with stage, age and lymph node metastasis, 15 Gomes et al reported no correlation between MMP-7 levels and clinicopathologic variables. 16 In the present study, we did not find any significant differences between early and stages of the disease in terms of tissue MMP-7 levels. Maurel et al reported that elevated levels of MMP-7 in serum might be evaluated as signs for poor prognosis in patients with advanced CRC.…”

Metalloproteinases and colorectal cancer. Correlation of gene expression and clinical-pathological parameters

“…A common mechanism for breaking these barriers is believed to be the action of proteolytic enzymes. Evidence suggests that proteinases, specifically MMPs, are involved in this process and that these proteins can be used as prognostic markers of colorectal cancer 8,15,18 .…”

“…In most human cancers, MMP expression and activity are high when compared to normal tissue. This has also been demonstrated in CCR, and MMPs can be used as tumor markers to prevent tumor growth, invasion and metastasis 6,9,15 .…”