Title
Contribution of plasminogen activators and their inhibitors to the survival prognosis of patients with Dukes' stage B and C colorectal cancer
Author
Gaubius Instituut TNO
Ganesh, S.
Sier, C.F.M.
Heerding, M.M.
van Krieken, J.H.J.M.
Griffioen, G.
Welvaart, K.
van de Velde, C.J.H.
Verheijen, J.H.
Lamers, C.B.H.W.
Verspaget, H.W.
Publication year
1997
Abstract
Despite the advances in pre-, peri- andpost-operative medical care of colorectal carcinoma patients, the prognosis has improved only marginally over recent decades. Thus, additional prognostic indicators would be of great clinical value to select patients for adjuvant therapy. In previous studies we found that colorectal carcinomas have a marked increase of the urokinase-type of plasminogen activator (u-PA), and the inhibitors PAI-1 and PAI-2, whereas the tissue-type plasminogen activator (t-PA) is found to be decreased in comparison with adjacent normal mucosa. In the present study we evaluated the prognostic value of several plasminogen activation parameters, determined in both normal and carcinomatous tissue from colorectal resection specimens, for overall survival of 136 Dukes' stage B and C colorectal cancer patients, in relation to major clinicopathological parameters. Uni- and multivariate analyses indicated that a high PAI-2 antigen level in carcinoma, a low t-PA activity and antigen level and a high U-PA/t-PA antigen ratio in adjacent normal mucosa are significantly associated with a poor overall survival. A high ratio of u-PA antigen In the carcinomas and t-PA antigen in normal mucosa, i.e. u-PA(C)/t-PA(N), was found to be predictive of a poor overall survival as well. All these parameters were found to be prognostically independent of the clinicopathological parameters. Multivariate analysis of combinations of these prognostically significant plasminogen activation parameters revealed that they are important independent prognostic indicators and have in fact a better prognostic value than their separate components. Based on these combined parameters, subgroups of patients with Dukes' stage B and C colorectal cancer could be identified as having either a high or a low risk regarding overall survival. In conclusion, these findings emphasize the relevance of the intestinal plasminogen activation system for survival prognosis of patients with colorectal cancer and, in the future might constitute a patent selection criterion for adjuvant therapy.
Subject
Aged
Colorectal Neoplasms
Data Interpretation, Statistical
Enzyme-Linked Immunosorbent Assay
Female
Histological Techniques
Humans
Male
Middle Aged
Plasminogen Activator Inhibitor 1
Plasminogen Activator Inhibitor 2
Plasminogen Activators
Plasminogen Inactivators
Prognosis
Spectrophotometry
Survival Rate
Time Factors
Tissue Plasminogen Activator
Urinary Plasminogen Activator
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TNO identifier
233949
ISSN
0007-0920
Source
British Journal of Cancer, 75 (75), 1793-1801
Document type
article