Study of cyclooxygenase-2 in renal cell carcinoma
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.
Available from: ncbi.nlm.nih.gov
- "Some previous studies have reported that the degree of COX-2 expression is relatively higher in RCC than the normal kidney.26,27 This is in agreement with our results that there was a minimal degree of COX-2 expression in non-neoplastic renal parenchyma, thus suggesting a role of COX-2 in the development of CCRCC. "
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ABSTRACT: The prognostic value of cyclooxygenase-2 (COX-2) in human renal cell carcinoma (RCC) remains unclear. The purposes of this study are to elucidate the clinical significance of COX-2 in clear cell RCC (CCRCC) and to assess the treatment effect of COX-2 inhibition on CCRCC cell lines.
Using tumor samples obtained from 137 patients who had undergone nephrectomy at Seoul National University Hospital, we evaluated COX-2 expression on immunohistochemistry. Moreover, we performed the cell proliferation assay using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) and cell invasion assay. Thus, we evaluated the effect of meloxicam, an inhibitor of COX-2, in two human CCRCC cell lines.
Cancer-specific survival (p=0.038) and progression-free survival (p=0.031) were shorter in the COX-2 high expression group. A multivariate logistic regression model showed that COX-2 expression was an independent risk factor for pTNM stage and Fuhrman nuclear grade. The MTT assay revealed that COX-2 inhibition led to the suppression of the proliferation of CCRCC cell lines. Moreover, it also reduced their invasion capacity.
This study postulates that COX-2 is a poor prognostic indicator in human CCRCC, suggesting that COX-2 inhibition can be a potential therapy in CCRCC.
Available from: PubMed Central
- "Although the COX-2 is highly expressed in canine RCC,16 it is down-regulated in RCC in the Eker (TSC2 gene mutant) rat model.17 The COX-2 is highly expressed in human RCC, but the results of its correlation with tumor stage and grade have been contradictory.18,19 "
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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.
Available from: Minna Kankuri
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