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.
OBJECTIVE
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).


METHODS
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.
Miyata
Yasuyoshi
Y
Department of Urology, Nagasaki University School of Medicine, Japan. int.doc.miya@m3.dion.ne.jp
Iwata
Takahisa
T
Ohba
Kojiro
K
Kanda
Shigeru
S
Nishikido
Masaharu
M
Kanetake
Hiroshi
H
D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000378:metabolism* / Q000556:secondary*; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000556:secondary*; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000096:biosynthesis*; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7