Urokinase system expression in gastric carcinoma

Abstract

BACKGROUND.The prognostic relevance of urokinase-type plasminogen activator (u-PA), u-PA receptor (u-PAR), and plasminogen activator inhibitor 1 (PAI-1) in gastric carcinoma was demonstrated in an independent patient series. To the authors' knowledge,the roles of these activators as predictors of aggressive phenotypes in preoperative biopsies, Helicobacter pylori infection, and intestinal metaplasia have to date not been investigated simultaneously in resected tumors. The objectives of the current study were 1) to demonstrate the prognostic relevance of u-PA, u-PAR, and PAI-1 in an independent series; 2) to evaluate u-PA system expression in preoperative biopsy specimens compared with resected tumors; and 3) to evaluate u-PA system expression in intestinal metaplasias and samples with H. pylori infection. METHODS.In 104 patients with gastric carcinoma (median follow-up, 68 mos), u-PA, u-PAR, and PAI-1 in tumors and metaplasias were evaluated immunohistochemically. Preoperative biopsies were evaluated in a subset of patients. Patients were screened for H. pylori (urease) and tumor cells in bone marrow (u-PAR/ CK18).RESULTS. u-PA and PAI-1 were confirmed as independent prognostic parameters, and u-PAR was associated with a trend toward a poor prognosis. u-PA system tumor expression was found to be correlated significantly with u-PAR in disseminated tumor cells and H. pylori-infected tumors, implicating a role of H. pylori in protease induction. There was a significant correlation noted between u-PA system staining between preoperative biopsies and the results in resected tumors. The expression of u-PAR and PAI-1 in intestinal metaplasias was found to be associated significantly with advanced tumor stage (depth of invasion; pathologic tumor status) and lymph node involvement (pathologic lymph node status) and was correlated significantly with u-PA system expression in tumors. CONCLUSIONS.To the author's know the current study is the first to date to demonstrate that u-PA system expression may serve as a predictor of risk in intestinal metaplasias and preoperative biopsies, implicating consequences for neoadjuvant therapy. The independent impact on recurrence and survival and a correlation with u-PAR-expression of minimal residual disease were identified in

The urokinase plasminogen activation system in gastroesophageal cancer: A systematic review and meta-analysis

“…Hazard ratios directly extracted for 3 studies [7, 11, 22]. The multivariate HR was used when univariate value was not provided [22].…”

“…The multivariate HR was used when univariate value was not provided [22]. When only subgroup outcome data (tumour core or peripheral zone) were available, the results for peripheral “invasion” zone were used [7, 11].…”

“…Only 4 studies [22, 27–29] were deemed low risk in all bias domains. Fourteen studies did not clearly define the study population [7, 12, 13, 30–40] and 11 studies did not report completeness of followup [7, 12, 13, 30–33, 36, 38, 39, 41].…”

Role of Urokinase Receptor in Tumor Progression and Development

“…In breast cancer, elevated uPAR expression is used as an independent prognostic marker of shortened relapse-free survival 34-36. In gastric cancer, high uPAR level in primary tumors is the indicator of aggressive cancer type 37, 38.…”

Reverse-Phase Protein Array Analysis to Identify Biomarker Proteins in Human Pancreatic Cancer

“…PAI-1, encoded by SERPINE1 , is a member of the serpin family of serine protease inhibitors and is one of the key regulators of tumor invasion and metastasis [52,53]. Overexpression of PAI-1 has been observed in oral squamous cell carcinoma, identified as a potential marker of initial invasion [54], and correlated with a poor prognosis [54,55].…”