Expression of Cyclooxygenase-2 Protein in Colorectal Carcinomas

Joo, Young‐Eun; Kim, Hyunsoo; Min, Sang-Woon; Lee, Wan‐Sik; Park, Chang-Hwan; Park, Chang‐Soo; Choi, Sung‐Kyu; Rew, Jong Sun; Kim, Sei-Jong

doi:10.1385/ijgc:31:1-3:147

Cited by 43 publications

(44 citation statements)

References 28 publications

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“…In adjacent normal colorectal tissue in the same slide the COX-2 protein was not observed. These results suggest that increased expression of COX-2 is associated with CRC [12] . SNPs in the COX-2 promoter may alter the enzyme activity of COX-2 by differential regulation of COX-2 expression, which may influence the risk of the development of CRC [7][8][9] .…”

Section: Discussionmentioning

confidence: 63%

COX-2 polymorphisms -765G→C and -1195A→G and colorectal cancer risk

Hoff¹,

Morsche²,

Roelofs³

et al. 2009

WJG

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AIM:To determine the possible modulating effect of the COX-2 polymorphisms, -765G→C and -1195A→G , on the risk of colorectal cancer (CRC) in a Dutch population. METHODS:This case-control study includes 326 patients with CRC and 369 age-and gender-matched controls. Genotypes of the COX-2 polymorphisms -765G→C and -1195A→G were determined by polymerase chain reaction-based restriction fragment length polymorphism. COX-2 genotypes and haplotypes were analyzed and odds ratios with 95% confidence intervals were estimated by logistic regression. RESULTS:The -765GG genotype was associated with an increased risk of developing CRC (OR, 1.45; 95% CI, 1.03-2.04). No significant difference was observed in the genotype distribution of the -1195A→ G polymorphism between patients and controls. The GG/AC haplotype was present significantly less often in patients than in controls (OR 0.44; 95% CI, 0.22-0.85).When the AC , AG and GG haplotypes were investigated separately, the AC haplotype showed a tendency to be less frequent in patients than in controls (OR(AG/AC) 0.78; 95% CI, 0.57-1.06). CONCLUSION:The -765GG genotype is associated with an increased risk of developing CRC and the GG/ AC haplotype seems to protect against CRC. These findings suggest a modulating role for the COX-2 polymorphisms -765G→C and -1195A→G in the development of CRC in a Dutch population.

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Section: Discussionmentioning

confidence: 63%

COX-2 polymorphisms -765G→C and -1195A→G and colorectal cancer risk

Hoff¹,

Morsche²,

Roelofs³

et al. 2009

WJG

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“…Also, some authors that used immunohistochemical analysis method claimed that Cox-2 may be involved in tumorigenesis but lack a prognostic significance for colorectal cancer patients (18,23,(35)(36)(37). At this point, it is considered that tumor invasiveness, frequent metastasis, and expression in larger tumors are responsible for the worse prognosis for patients bearing Cox-2-positive tumors (14).…”

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase-2 Expression

Soumaoro

Uetake

Higuchi

et al. 2004

Clinical Cancer Research

230

172

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Purpose: Recent studies have shown that cyclooxygenase (Cox)-2 may be involved in colorectal carcinogenesis. We aimed to determine whether Cox-2 expression in itself can predict outcome of colorectal cancer patient after surgery. In addition, the expression of Cox-1 was also evaluated.Experimental Design: Tissue samples of primary and secondary tumors from 288 patients undergoing surgical resections for colorectal adenocarcinoma were immunohistochemically examined for Cox-2 and Cox-1 expressions. The specimens were graded based on the intensity and extent of staining; then, the correlations between Cox-2 and Cox-1 expressions with clinicopathologic parameters and survival time were analyzed.Results: Expression of Cox-2 was positive in 70.8% of primary tumor, 92.0% of lymph node metastases, 100.0% of hepatic metastases, and was significantly associated with tumor size, depth of invasion, lymph node metastasis, vessels invasion, stage and recurrence. In contrast, Cox-1 was positive in 42.7% of primary tumor, 84.0% of lymph node metastases, 37.5% hepatic metastases, and was associated with only tumor size. Patients with Cox-2-positive tumors had a significant shorter survival time than those with negative tumors did (P ‫؍‬ 0.0006 by log-rank test); and, in a multivariate analysis, Cox-2 was an independent prognostic factor (P ‫؍‬ 0.0103; relative risk 4.114; 95% confidence interval, 1.397-12.120). Cox-1 status had no statistically effect on patient survival time.Conclusions: Elevated Cox-2 expression, but not that of Cox-1, was significantly associated with reduced survival and recognized as an independent prognostic factor in our cohort of colorectal cancer patients.

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“…We used the scoring system recommended by Remmele and Stegner (26). It is established internationally for the evaluation of breast cancer, and it is very similar to scoring systems used in other studies about COX-2 in colorectal cancer (17,19). Our staining method (avidin-biotin complex method of Hsu et al;ref.…”

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase-2 Expression in Human Colorectal Cancer Is Unrelated to Overall Patient Survival

Fux

Schwab²,

Thon

et al. 2005

Clinical Cancer Research

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Purpose: Cyclooxygenase-2 (COX-2) expression in human colorectal cancer and adenoma tissue seems to be higher than in normal mucosa. However, data about the relation between COX-2 expression and patient survival are inconclusive as yet. Therefore, we studied COX-2 expression in surgery tissue and survival time in a cohort of 747 colorectal cancer patients. Experimental Design: Surgical specimens of primary colorectal cancer from 747 individuals were immunostained for COX-2 and evaluated under a transmission light microscope. COX-2 expression was scored according to intensity and extent of staining, resulting in the COX-2 immunoreactivity score (IRS-COX2). All possible cutoff points for IRS-COX2 were analyzed for a relation between COX-2 expression and patient survival. Results: Both univariable and multivariable analysis have shown that the COX-2 expression in human tumor epithelial cells was unrelated to overall patient survival and to disease-free survival, irrespectively of the cutoff point for IRS-COX2. The survival rates for 1, 3, 5, and 10 years were 81.0%, 66.8%, 60.2%, and 49.8% (median: 117.3 months; 95% confidence interval, 102.3-132.0), respectively. In the multivariable analysis, only node and metastasis were significantly related to overall patient survival. Similar results were obtained when stage IV and rectal cancer patients were excluded from the analysis. Conclusions: COX-2 expression in tumor epithelial cells does not seem to be related to survival of colorectal cancer patients. Besides COX-2, there are several targets, such as the peroxisome proliferator^activated receptors, that are involved in carcinogenesis and may be modulated by nonsteroidal anti-inflammatory drugs. Further studies are needed to determine their prognostic relevance.

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Expression of Cyclooxygenase-2 Protein in Colorectal Carcinomas

Abstract: These results suggest that COX-2 expression may play an important role in the evolution of colon carcinogenesis. However, further studies are needed to determine the prognostic relevance of COX-2.

Cited by 43 publications

References 28 publications

COX-2 polymorphisms -765G→C and -1195A→G and colorectal cancer risk

COX-2 polymorphisms -765G→C and -1195A→G and colorectal cancer risk

Cyclooxygenase-2 Expression

Cyclooxygenase-2 Expression in Human Colorectal Cancer Is Unrelated to Overall Patient Survival

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