Expression of cyclooxygenase-2 in renal cell carcinoma: correlation with tumor cell proliferation, apoptosis, angiogenesis, expression of matrix metalloproteinase-2, and survival.
OBJECTIVE
Cyclooxygenase (COX)-2 plays an important role in tumor cell proliferation, resistance to apoptosis, angiogenesis, and invasion in various malignant tumors. However, the relationships between COX-2 expression and these biological processes, clinicopathological features, and survival rate in patients with renal cell carcinoma are not clear.


METHODS
Tumor sections surgically removed from 131 patients were examined for COX-2 expression by immunohistochemistry. We also examined Ki-67 labeling index, apoptotic index, microvessel density, and matrix metalloproteinase (MMP)-2 expression, and correlated COX-2 expression with various clinicopathological features and survival.


RESULTS
Of 131 sections, 70 (53.4%) were positive for COX-2 expression. COX-2 expression was associated significantly with various clinicopathological features, and correlated with the Ki-67 labeling index, microvessel density, and MMP-2 expression (P < 0.01), but not with the apoptotic index (P = 0.054). COX-2 expression was also identified as an independent risk factor for large tumor size (>7 cm) in multivariate logistic regression model. COX proportional hazards analysis showed that distant metastasis and high T stage were independent prognostic factors [odds ratio (OR), 9.41; 95% confidence interval (CI), 2.16-41.11; P < 0.01 and OR, 5.19; 95% CI, 1.02-26.54; P = 0.048, respectively), whereas COX-2 expression was not (OR, 1.46; 95% CI, 0.24-9.00; P = 0.68).


CONCLUSIONS
COX-2 expression in patients with renal cell carcinoma is associated with several clinicopathological factors, and appeared to play an important role in tumor cell proliferation and MMP-2 expression, but is not a significant prognostic factor.
Department of Urology, Nagasaki University School of Medicine, Japan. int.doc.miyata@nifty.ne.jp
Yasuyoshi
Y
Miyata
Shigehiko
S
Koga
Shigeru
S
Kanda
Masaharu
M
Nishikido
Tomayoshi
T
Hayashi
Hiroshi
H
Kanetake
D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis; D002291:Carcinoma, Papillary / Q000098:blood supply / Q000201:enzymology / Q000401:mortality; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000201:enzymology* / Q000401:mortality; D002455:Cell Division; D051546:Cyclooxygenase 2; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D007668:Kidney / Q000201:enzymology / Q000473:pathology; D007680:Kidney Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000401:mortality; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008565:Membrane Proteins; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000201:enzymology*; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D015996:Survival Rate
D014408:Biomarkers, Tumor; D007527:Isoenzymes; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D020778:Matrix Metalloproteinase 2