MMP-9 and Cathepsin B Expression in Tumor Budding as an Indicator of a More Aggressive Phenotype of Colorectal Cancer (CRC)

Abstract

Background: The aim of this study was to clarify the relationship between the expression of MMP-9 and Cathepsin B (CathB) at the main tumor mass and lymph node metastases and the presence of tumor budding and vascular invasion at the invasion front, as well as lymph node involvement. Patients and Methods: The immunohistochemical expressions of MMP-9 and CathB were studied in 55 specimens of colorectal adenocarcinomas (pT3, G2). A standard avidin-biotin immunoperoxidase staining method (ABCu-NCL) was performed on 4-μm paraffin-embedded tissue sections with a mouse anti-human MMP-9 and CathB monoclonal antibody. Results: Positive immunostaining for MMP-9 in the primary tumor was observed in 30/55 (54.6%) cases and in 29 cases (52.7%) for CathB. A statistically significant association was found between the expressions of MMP-9 and CathB in the primary tumor and lymph node involvement (p<0.01). The expression of CathB in the primary tumor was associated with the presence of tumor budding and vascular invasion (p<0.01); but no such association was found for MMP-9. The expressions of MMP-9 and CathB in buds were strongly associated with lymph node involvement (p<0.01). However, the presence of vascular invasion was significantly associated only with positive expression of CathB in the buds (p<0.01). Conclusion: If the presence of budding in the colorectal cancer invasive front indicates higher invasive potential, the present results seem to suggest the existence of a strong relationship between MMP-9 and CathB expressions in the buds and a more aggressive tumor phenotype.