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


CONCLUSIONS
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.
McKenna
Gregory J
GJ
Department of Surgery, Vancouver Hospital and Health Sciences Centre, University of British Columbia, Vancouver, British Columbia, Canada.
Meneghetti
Adam
A
Chen
Yong Liang
YL
Mui
Alice L F
AL
Ong
Christopher
C
Scudamore
Charles H
CH
McMaster
W Robert
WR
Owen
David A
DA
Chung
Stephen W
SW
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000368:Aged; D014670:Ampulla of Vater / Q000601:surgery; D003138:Common Bile Duct Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D005260:Female; D005544:Forecasting; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D015996:Survival Rate; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis*
D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9