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Cyclooxygenase-2 expression in right- and left-sided colon cancer: a rationale for optimization of cyclooxygenase-2
Aejaz Nasir1, Hans E Kaiser, David Boulware
1H. Lee Moffitt Cancer Center & Research Institute, University of South Florida, Tampa, USA.
Abstract:
Cyclooxygenase-2 (COX-2) has been identified as a potential target for prevention and therapy of human colorectal cancers (CRC) and other cancers. Because right-sided colon cancers (RSCCs) exhibit clinicopathologic and genetic differences from left-sided colorectal cancers (LSCRCs), determination of COX-2 status in these subsets of CRCs may be clinically relevant in designing COX-2 inhibitor trials for CRC and in subsequent assessment of objective therapeutic response to such therapy. Thirty-six primary CRC resection specimens (18 left, 18 right) from 36 patients were evaluated. Representative tumor sections were subjected to immunohistochemical analysis of COX-2. A semiquantitative system was used to score cytoplasmic COX-2 immunostaining. The tumors were considered COX-2 positive if more than 10% tumor cells showed COX-2 staining. Clinicopathologic and COX-2 data were compared for LSCRCs versus RSCCs. All 18 LSCRCs and 13 of 18 (72%) RSCCs were well to moderately differentiated. Overall rates of COX-2 positivity for the LSCRCs versus RSCCs were 67% (12 of 18) and 33% (6 of 18), respectively (P = 0.04). Furthermore, 11 of 12 (92%) COX-2 positive LSCRCs and 3 of 6 (50%) COX-2 positive RSCCs were stage II-IV at resection. All 12 COX-2 positive LSCRCs were associated with advanced primary tumor and 4 of 12 (33%) LCRCs had distant metastases. These associations could not be evaluated for the RSCCs because of the limited number of COX-2 positive cases. The more frequent expression of COX-2 in LSCRCs as compared with RSCCs supports the hypothesis that COX-2 expression may be related to genetic alterations specific to right- or left-sided CRCs. Further studies are needed to elucidate such relationships. Our data also suggest that stratification of patients with CRC into right- and left-sided subsets may be important in optimal patient selection for COX-2 inhibitor therapy and for subsequent assessment of objective therapeutic response.
Insights
Cyclooxygenase-2 (COX-2) is more frequently expressed in left-sided colorectal cancers (LSCRCs) than right-sided colorectal cancers (RSCCs). This finding suggests COX-2 status may be important for selecting patients for COX-2 inhibitor therapy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Cyclooxygenase-2 (COX-2) is a potential therapeutic target for human colorectal cancers (CRC).
- Right-sided (RSCCs) and left-sided colorectal cancers (LSCRCs) exhibit distinct clinicopathologic and genetic features.
- Understanding COX-2 expression differences between RSCCs and LSCRCs is crucial for targeted therapies.
Purpose of the Study:
- To compare COX-2 expression in LSCRCs versus RSCCs.
- To investigate the clinical relevance of COX-2 status in different colorectal cancer subsets.
- To inform patient selection for COX-2 inhibitor trials and therapeutic response assessment.
Main Methods:
- Immunohistochemical analysis of COX-2 expression in 36 primary CRC resection specimens (18 LSCRCs, 18 RSCCs).
- Semiquantitative scoring of cytoplasmic COX-2 immunostaining.
- Comparison of COX-2 positivity rates and clinicopathologic data between LSCRCs and RSCCs.
Main Results:
- Overall COX-2 positivity was 67% in LSCRCs versus 33% in RSCCs (P=0.04).
- A higher proportion of COX-2 positive LSCRCs (92%) were advanced stage (II-IV) compared to RSCCs (50%).
- COX-2 positive LSCRCs were associated with advanced primary tumors and distant metastases.
Conclusions:
- Frequent COX-2 expression in LSCRCs supports its potential role in specific genetic alterations.
- Stratifying CRC patients by tumor location (right vs. left) may optimize patient selection for COX-2 inhibitor therapy.
- Further research is needed to elucidate COX-2's relationship with CRC sidedness and therapeutic response.
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