Predictive value of lymph node and tumor matrix metalloproteinase expression in the analysis of metastatic periampullary tumors.

BACKGROUND AND OBJECTIVES: Matrix metalloproteinases (MMP) are endogenous peptidases capable of degrading various components of the basement membrane. The ability of malignant epithelial cells to degrade extracellular matrix and basement membrane is an important step in the process of metastatic invasion. In this study, we prospectively compared the outcome of patients undergoing laparotomy for resection of periampullary malignancies with lymph node and tumor MMP expression to determine if there was a correlation between metalloproteinase expression and patient outcome.

METHODS: Sixteen patients undergoing operation were followed prospectively. Expression of MMP-2 and -9 and their inhibitors TIMP (tissue inhibitor of matrix metalloproteinase) -1 and -2 were measured in lymph node and tumor samples by semiquantitative PCR analysis.

RESULTS: All patients who died from their disease process had significantly greater MMP-2 expression in their lymph nodes relative to TIMP-2 expression. In contrast, patients with prolonged disease-free survival had decreased nodal MMP-2/TIMP-2 expression (P = 0.001). Patients with relatively higher MMP-2/TIMP-2 expression in their tumors also had a worse prognosis (P = 0.06).

CONCLUSION: The data demonstrate that the mRNA expression of MMPs and TIMPs in the draining lymph node of patients with periampullary adenocarcinomas may hold prognostic significance for patient survival. This prognostic information may be of use in patients when planning future adjuvant therapies.