Matrix metalloproteinase-7 and matrix metalloproteinase-9 are associated with unfavourable prognosis in superficial oesophageal cancer

Abstract

If oesophageal carcinoma is detected in the superficial stage, the prognosis is better than for advanced oesophageal carcinoma. But the factors which predict the prognosis and treatment policy remain unclear. Matrix metalloproteinase-7 (MMP-7) and matrix metalloproteinase-9 (MMP-9) have been reported to have close associations with tumour invasion and metastasis. In this study, we retrospectively studied the relations between MMP-7 and MMP-9 expression in immunohistochemistry, clinicopathologic factors, and prognosis in 55 superficial oesophageal carcinomas. MMP-7 and MMP-9 expression occurred in 23.6% and 47.3% of the patients, respectively. MMP-7 expression was significantly correlated with the presence of nodal metastasis (P ¼ 0.004). MMP-9 expression was significantly correlated with the depth of tumour invasion (P ¼ 0.004), lymphatic permeation (P ¼ 0.001), nodal metastasis (P ¼ 0.049), and pathologic differentiation grade (P ¼ 0.003). By the log-rank test, MMP-7 expression and MMP-9 expression on the invasive front were related to the prognosis. In multivariate analysis, MMP-9 expression on the invasive front was an independent prognostic indicator. The combined expression of MMP-7 and MMP-9 may be a good marker for the degree of malignancy of oesophageal cancer and for the presence of lymphatic metastasis.

Prognostic significance of matrix metalloproteinase‐7 in epithelial ovarian cancer and its relation to β‐catenin expression

“…Our study as well as reports on gastrointestinal cancers showing correlation between MMP-7 and patient survival were done with an antibody against the proform of MMP-7. 33,34,38 However, according to our results, an antibody recognizing both pro and active forms gives comparable results.…”

The role of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the development of esophageal cancer

“…It has been proved that these enzymes are involved in the development of many malignant neoplasms: gastric, colorectal, pancreatic and breast cancer [40][41][42][43]. High MMP-9 protein expression in tumor tissues of EC patients has been shown in several studies [4,18,[44][45][46][47]. Percentages of MMP-9 positive immunostaining (diagnostic sensitivity) in esophageal cancer tissue reached 78% in the study by Murray et al [44] and increased with tumor stage.…”

“…Microvessel density in patients with highly positive staining for MMP-9 was higher than in those with negative or weak staining for MMP-9 [4], which suggests that the expression of MMP-9 possibly could offer additional information about the aggressiveness and activity of esophageal carcinoma lesions. Moreover, high expression of MMP-9 in cancer tissue may be a negative prognostic factor of EC patients' survival [45].…”

Arsenic trioxide prevents radiation-enhanced tumor invasiveness and inhibits matrix metalloproteinase-9 through downregulation of nuclear factor κB

“…MMP activity is tightly controlled by endogenous inhibitors, including a2-macroglobulin, tissue inhibitors of metalloproteinases (TIMPs), and the membranebound inhibitor RECK (Baker et al, 2002). The expression and activity of MMPs are increased in almost every type of human cancer, and this is often associated with advanced tumor stage and poor survival (Sienel et al, 2003;Tanioka et al, 2003;Zucker and Vacirca, 2004). Recent studies demonstrated that MMPs also promote survival of cancer cells by liberating insulin growth factor and by cleavage of FAS ligand (Miyamoto et al, 2004;Strand et al, 2004).…”