Immunoexpression of Metalloproteinases 2 and 14 and TIMP-2 Inhibitor in Main Types of Primary Gastric Carcinomas and Lymph Node Metastasis

Metalloproteinase-2 (MMP-2) and −14 (MMP-14) and the tissue inhibitor of metalloproteinases type 2 (TIMP-2) participate in epithelial-mesenchymal transition and tumor progression in many cancers. However, the correlation between these enzymes in gastric cancer and the metastatic potential to their respective lymph node needs to be determined. Here, we evaluated the expression of these enzymes in gastric carcinoma and lymph node metastases and their possible involvement in tumor progression. Histological samples from 83 patients with gastric cancer and their respective lymph nodes were used. MMP-2, MMP-14 and TIMP-2 immunoexpression was scored. TIMP-2 expression in tumor-associated macrophages occurred more frequently than in normal mucosa ( P = 0.0128). Female tumor samples presented higher MMP-2 expression ( P = 0.0248), while TIMP-2 occurred mainly in patients over 50 years old ( P = 0.0034). MMP-2 was higher expressed in primary tumor macrophages than in neoplastic cells ( P = 0.0118), and was also seen in macrophages from metastatic-affected lymph nodes of intestinal and diffuse histotypes ( P = 0.0006). MMP-2, MMP-14 and TIMP-2 expression in mononuclear cells might be correlated with progression of gastric cancer. MMP-14 production by macrophages appears to be more involved in diffuse gastric cancer progression.