McKenna Gregory J, Meneghetti Adam, Chen Yong Liang, Mui Alice L F, Ong Christopher, Scudamore Charles H, McMaster W Robert, Owen David A, Chung Stephen W
Department of Surgery, Vancouver Hospital and Health Sciences Centre, University of British Columbia, Vancouver, British Columbia, Canada.
J Surg Oncol. 2005 Jun 15;90(4):239-46. doi: 10.1002/jso.20258.
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.
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.
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).
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.
基质金属蛋白酶（MMP）是一类能够降解基底膜各种成分的内源性肽酶。恶性上皮细胞降解细胞外基质和基底膜的能力是转移侵袭过程中的重要一步。在本研究中，我们前瞻性地比较了接受剖腹手术切除壶腹周围恶性肿瘤患者的淋巴结和肿瘤MMP表达情况，以确定金属蛋白酶表达与患者预后之间是否存在相关性。
对16例接受手术的患者进行前瞻性随访。通过半定量PCR分析测定淋巴结和肿瘤样本中MMP - 2和 - 9及其抑制剂基质金属蛋白酶组织抑制剂（TIMP） - 1和 - 2的表达。
所有因疾病进展死亡的患者，其淋巴结中MMP - 2表达相对于TIMP - 2表达显著更高。相比之下，无病生存期延长的患者淋巴结中MMP - 2/TIMP - 2表达降低（P = 0.001）。肿瘤中MMP - 2/TIMP - 2表达相对较高的患者预后也较差（P = 0.06）。
数据表明，壶腹周围腺癌患者引流淋巴结中MMP和TIMP的mRNA表达可能对患者生存具有预后意义。在规划未来辅助治疗时，该预后信息可能对患者有用。
