NDLI: Tumor-associated proteases and inhibitors in gastric cancer: analysis of prognostic impact and individual risk protease patterns

Content Provider	Springer Nature Link
Author	Allgayer, Heike Babic, Rudolf Uwe Grützner, Klaus Beyer, Bianca C. M. Tarabichi, Anwar Wilhelm Schildberg, Friedrich Heiss, Markus Maria
Copyright Year	1998
Abstract	Expression of proteolytic parameters of the urokinase-type plasminogen activator (uPA) system [uPA receptor (uPA-R), plasminogen activator inhibitor (PAI)-1] has been proven to be an independent prognostic parameter in cancer. However, it has not been considered that the uPA system is interacting with several other protease/inhibitor systems, neither has a comparable prognostic role of these factors been investigated. Moreover, studies evaluating specific protease patterns indicating high individual risk are missing completely. Therefore, in a consecutive prospective series of 203 gastric cancer patients, the expression of activators (plasminogen, tPA, MMP-2, cathepsin D, antithrombin 3) and inhibitors (a-2-antiplasmin, a-2-macroglobulin, a-1-antitrypsin, a-1-antichymotrypsin) of proteolysis was studied immunohistochemically in the tumor epithelium semiquantitatively (score 0-3) in addition to the uPA system. Kaplan-Meier analysis (median time of follow-up 31 months) revealed a significant association of cathepsin D (P = 0.0042), a-2-macroglobulin (P = 0.0281) and antitrypsin (P = 0.0372) with disease-free survival and of cathepsin D (P = 0.0018), antitrypsin (P = 0.0112) and antichymotrypsin (P = 0.0002) with overall survival. Multivariate Cox analysis performed to correct these results for relative impact of the uPA system and established prognostic factors showed PAI-1 (disease-free survival: P = 0.002, relative risk 1.86; overall survival: P = 0.005, relative risk 1.39), pT and pN as independent parameters. Cathepsin D was shown to have an independent impact on disease-free survival (P = 0.020, relative risk 2.98). Comparative chi-square analysis of cases with poor and good prognoses revealed that in patients with good clinical outcome, inhibitors of proteolysis are correlated significantly, whereas in patients with poor prognosis activators of proteolysis are significantly associated preferentially and significant correlations with the uPA-R are dominan t. For detailed pattern analysis, stepwise overall Kaplan-Meier analyses were performed in subgroups of high uPA-R-, uPA-, PAI-1-and cathepsin D expression for two additional proteases each. From these analyses, the combination of high (score 2/3) expression of uPA-R, PAI-1, antichymotrypsin and a-2-macroglobulin was identified as a high-risk pattern, representing parameters known to be essential for uPA-R internalization and recycling. This suggests some of the uPA-associated proteases and inhibitors investigated as univariate prognostic parameters in gastric cancer. Cathepsin D is a new independent parameter for disease-free survival. The study further demonstrates that a protease pattern promoting uPA-R recycling in tumor cells especially indicates high individual risk tumors in gastric cancer. © Rapid Science 1998
Starting Page	62
Ending Page	73
Page Count	12
File Format	PDF
ISSN	02620898
Journal	Clinical & Experimental Metastasis
Volume Number	16
Issue Number	1
e-ISSN	15737276
Language	English
Publisher	Kluwer Academic Publishers
Publisher Date	1998-01-01
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Hematology Surgical Oncology Pathology
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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