Study of cyclooxygenase-2 in renal cell carcinoma
ABSTRACT Cyclooxygenase (COX)-2 plays an important role in the development of various cancers due to its angiogenetic function. As the expression of COX-2 is up-regulated in human colorectal carcinoma and other cancers, we investigated the expression of COX-2 in human renal cell carcinoma (RCC) tissues. One hundred and eight specimens were obtained from patients with RCC, and 20 from normal kidney (NK) tissues. Immunohistochemistry, using affinity purified anti-bodies against human COX-2, and RT-PCR to study the COX-2 mRNA expression were carried out. We also examined whether or not there was a significant difference in the expression of COX-2 among grades (G1, G2, G3) and stages (pT1, pT2, pT3a, pT3b) in RCC. While no marked expression of COX-2 was observed in the NK tissues, a significantly strong expression of COX-2 was detected in RCC tissues. The extent and intensity of immunoreactive COX-2 polypeptides in cancer cells were statistically greater than those of cells from normal kidney tissues. However, no marked difference was seen among grades or between stages. These results demonstrate that the generated COX-2 in human renal cell carcinoma plays an important role in the proliferation of malignant renal cells.
- SourceAvailable from: doria.fi
- [Show abstract] [Hide abstract]
ABSTRACT: The aim of this study was to investigate the relationship of cyclooxygenase (COX)-2 and p53 expression with prognosis in patients with conventional renal cell carcinoma (RCC). Formalin-fixed, paraffin-embedded tissue sections of conventional RCC from 92 patients, who had undergone radical nephrectomy, were examined for COX-2 and p53 expression by immunohistochemistry and compared with clinicopathological variables. The COX-2 expression significantly correlated only with tumor size (p=0.049), whereas the p53 expression profoundly correlated with the TNM stage (p=0.024), M stage (p=0.001), and metastasis (synchronous or metachronous; p=0.004). The COX-2 overexpression did not significantly associate with p53 positivity (p=0.821). The survival rate of patients correlated with the p53 expression (p<0.0001) but not with the COX-2 expression (p=0.7506). Multivariate analyses indicated that tumor size, M stage, and p53 expression were independent prognostic factors for cancer-specific survival. The COX-2 expression was not an independent factor. These results show that the increased expression of p53 was associated with metastasis and a worse prognosis in conventional RCC, which suggests that p53 might have played an important role in the progression of conventional RCC. The increased expression of COX-2 was associated only with tumor size, but may not be an important prognostic factor in conventional RCC. No association was observed between COX-2 overexpression and p53 positivity in conventional RCC.Yonsei Medical Journal 03/2005; 46(1):133-40. DOI:10.3349/ymj.2005.46.1.133 · 1.26 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Cyclooxygenase-2 (COX-2) plays a major role in the development of cancer through numerous mechanisms. COX-2 is expressed in the majority of renal cell carcinoma (RCC) tumors and correlates with stage, grade, and microvessel density. Based on potential additive or synergistic antitumor effects, interferon-alpha (IFNalpha) and celecoxib, an oral COX-2 inhibitor, were given to metastatic RCC patients in a Phase II trial. Patients with untreated, metastatic RCC received IFNalpha 3 million units (MU) daily and celecoxib 400 mg orally (p.o.) twice daily continuously until disease progression or unacceptable toxicity. Pretreatment, paraffin-embedded RCC tumor samples were immunohistochemically stained for COX-2 expression and plasma basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels were assayed to determine predictive or prognostic potential. There were three partial responses among 25 patients treated (objective response rate, 12%; 95% confidence interval [CI], 3-31%). The observed median time to disease progression (TTP) for the entire cohort was 3.3 months. A significant association between maximal COX-2 staining and clinical response was observed: all patients who experienced an objective response demonstrated 3+ COX-2 tumor immunostaining (trend test: P=0.03). Therapy was well tolerated without cardiac or other notable toxicity. The addition of celecoxib to IFNalpha did not increase the objective response rate or TTP of this unselected cohort. Maximal COX-2 tumor immunostaining may identify RCC patents more likely to achieve clinical benefit with COX-2 inhibition in combination with IFNalpha. Further investigation of this combination in 3+ COX-2-overexpressing RCC tumors is warranted.Cancer 02/2006; 106(3):566-75. DOI:10.1002/cncr.21661 · 4.90 Impact Factor