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Urokinase system expression in gastric carcinoma: prognostic impact in an independent patient series and first evidence of predictive value in preoperative biopsy and intestinal metaplasia specimens.
Cancer. 2006 Mar 01; 106(5):1026-35.C

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 this independent series.

Authors+Show Affiliations

Department of Surgery Grosshadern, Ludwig-Maximilians-University, Munich, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16435385

Citation

Beyer, Bianca C M., et al. "Urokinase System Expression in Gastric Carcinoma: Prognostic Impact in an Independent Patient Series and First Evidence of Predictive Value in Preoperative Biopsy and Intestinal Metaplasia Specimens." Cancer, vol. 106, no. 5, 2006, pp. 1026-35.
Beyer BC, Heiss MM, Simon EH, et al. Urokinase system expression in gastric carcinoma: prognostic impact in an independent patient series and first evidence of predictive value in preoperative biopsy and intestinal metaplasia specimens. Cancer. 2006;106(5):1026-35.
Beyer, B. C., Heiss, M. M., Simon, E. H., Gruetzner, K. U., Babic, R., Jauch, K. W., Schildberg, F. W., & Allgayer, H. (2006). Urokinase system expression in gastric carcinoma: prognostic impact in an independent patient series and first evidence of predictive value in preoperative biopsy and intestinal metaplasia specimens. Cancer, 106(5), 1026-35.
Beyer BC, et al. Urokinase System Expression in Gastric Carcinoma: Prognostic Impact in an Independent Patient Series and First Evidence of Predictive Value in Preoperative Biopsy and Intestinal Metaplasia Specimens. Cancer. 2006 Mar 1;106(5):1026-35. PubMed PMID: 16435385.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Urokinase system expression in gastric carcinoma: prognostic impact in an independent patient series and first evidence of predictive value in preoperative biopsy and intestinal metaplasia specimens. AU - Beyer,Bianca C M, AU - Heiss,Markus Maria, AU - Simon,Erich H, AU - Gruetzner,Klaus-Uwe, AU - Babic,Rudolf, AU - Jauch,Karl-Walter, AU - Schildberg,Friedrich-Wilhelm, AU - Allgayer,Heike, PY - 2006/1/26/pubmed PY - 2006/3/29/medline PY - 2006/1/26/entrez SP - 1026 EP - 35 JF - Cancer JO - Cancer VL - 106 IS - 5 N2 - 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 this independent series. SN - 0008-543X UR - https://www.unboundmedicine.com/medline/citation/16435385/Urokinase_system_expression_in_gastric_carcinoma:_prognostic_impact_in_an_independent_patient_series_and_first_evidence_of_predictive_value_in_preoperative_biopsy_and_intestinal_metaplasia_specimens_ L2 - https://doi.org/10.1002/cncr.21682 DB - PRIME DP - Unbound Medicine ER -