Abstract

The aim of this study was to evaluate the expression of matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) in prostate cancer in the main tumor mass and tumor cells at the positive margin as well as the influence of these biomarkers on the biochemical recurrence of the disease in prostatectomy patients. Tissue microarrays of 120 archival prostate carcinoma samples were immunohistochemically evaluated for MMP-2 and MMP-9 expression and compared with clinicopathological parameters. Tumors with positive surgical margins showed significantly higher overall expression of MMP-9 versus tumors with negative resection margins (P = 0.0121). MMP-9 expression was significantly elevated in tumors from patients who had biochemical recurrence (P = 0.0207). In the group of patients with negative margins, MMP-9 expression above the cut-off value was significantly associated with recurrence (P = 0.0065). Multivariate analysis indicated that MMP-9 is a good predictor of biochemical recurrence (odds ratio = 10.29; P = 0.0052). Expression of MMP-2 in tumor cells was significantly higher at the positive margins than in the main tumor mass (P = 0.0301). The present results highlight the potential value of MMP-2 and MMP-9 expression for predicting the behavior of prostate tumors after prostatectomy with both positive and negative surgical margins.

Highlights

  • Extensive studies of the matrix metalloproteinases (MMPs) indicate that a large number of MMP family factors play active roles in carcinogenesis and metastasis [1,2,3]

  • The aim of this study was to evaluate the expression of matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP9) in prostate cancer in the main tumor mass and tumor cells at the positive margin as well as the influence of these biomarkers on the biochemical recurrence of the disease in prostatectomy patients

  • The standard biomarkers that significantly predict the clinical and biochemical recurrence of prostate cancer are preoperative serum prostate-specific antigen (PSA), pathological grade according to Gleason score, positive surgical margins, and capsular incision adding up the following factors as of prognostic significance: presence of perineural, angiolymphatic, seminal vesicle invasion and extraprostatic tissue invasion

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Summary

Introduction

Extensive studies of the matrix metalloproteinases (MMPs) indicate that a large number of MMP family factors play active roles in carcinogenesis and metastasis [1,2,3]. Investigations of high MMP-9 levels in plasma or serum samples showed that MMP-9 expression may be associated with increased risk of recurrence and poor prognosis [18, 19]. The standard biomarkers that significantly predict the clinical and biochemical recurrence of prostate cancer are preoperative serum prostate-specific antigen (PSA), pathological grade according to Gleason score, positive surgical margins (with and without extraprostatic extension), and capsular incision adding up the following factors as of prognostic significance: presence of perineural, angiolymphatic, seminal vesicle invasion and extraprostatic tissue invasion. Cao et al addressed the issue of positive resection margins in radical prostatectomy and found that the Gleason score at the edge of the tumor resection is predictive of biochemical recurrence [21]. There are currently no studies on the predictive value of MMP expression on the edge of the resection in radical prostatectomy

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