Expression of matrix metalloproteinase-7 on cancer cells and tissue endothelial cells in renal cell carcinoma: prognostic implications and clinical significance for invasion and metastasis

Clin Cancer Res. 2006 Dec 1;12(23):6998-7003. doi: 10.1158/1078-0432.CCR-06-1626.

Abstract

Purpose: The expression of matrix metalloproteinase-7 (MMP-7) correlates with the malignant potential of various tumors and patient survival. We investigated the clinical and prognostic significance of MMP-7 expression in cancer cells and endothelial cells in human renal cell carcinoma (RCC).

Experimental design: We reviewed tissue samples of 156 patients with RCC who had undergone radical operation. MMP-7 expression was examined by immunohistochemistry. Sections containing MMP-7-positive vessels were also stained for CD34. The density of MMP-7-positive vessels was determined by a computer-aided image analysis system. Multivariate analysis was done to assess relevant variables for invasion, metastasis, and cause-specific survival.

Results: The proportion of MMP-7-expressing tumor cells were significantly higher (P < 0.001) than that of normal cells. MMP-7-positive vessels were considered blood vessels based on staining for CD34, and their density was increased in tumor areas. The proportion of MMP-7-expressing cancer cells and density of MMP-7-positive vessels correlated with grade, pathologic tumor stage, and metastasis. Multivariate analysis showed that MMP-7 expression on cancer cells correlated with pathologic tumor stage only, whereas MMP-7-positive vessel density correlated with metastasis only. The elevated status of MMP-7 in cancer tissues was an independent predictor for cause-specific survival (odds ratio, 8.61; P = 0.040) by multivariate analysis.

Conclusions: Our results showed that MMP-7 influences tumor progression by regulating invasion and angiogenesis. Multivariate analysis showed that MMP-7 status of cancer tissues was strong predictor of poor prognosis. Our results suggest that MMP-7 targeting treatment may be a potential target against RCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Renal Cell / diagnosis
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / secondary*
  • Cell Line, Tumor
  • Endothelial Cells / pathology*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / diagnosis
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / secondary*
  • Male
  • Matrix Metalloproteinase 7 / biosynthesis*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • Retrospective Studies
  • Survival Rate

Substances

  • MMP7 protein, human
  • Matrix Metalloproteinase 7