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Expression of cyclo-oxygenase-2 in gastrointestinal carcinoid tumors
Shigeaki Mizuno1, Kimitoshi Kato, Akemi Hashimoto
1Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Background:
Cyclo-oxygenase (COX)-2 overexpression is observed in various neoplasms and COX-2 inhibition has been attempted as prevention and/or therapy in these neoplasms. Carcinoid tumors are thought to arise from neuroendocrine cells and originate mainly in the gastrointestinal tract. Cyclo-oxygenase-2 is reportedly expressed in neuroendocrine cells of normal colorectal mucosa. The role of COX in carcinoids has not previously been investigated. The aim of the present paper was to clarify the expression of COX-1 and -2, and their role in human gastrointestinal carcinoids.
Methods:
Expression of COX-1 and -2 was studied immunohistochemically in 38 gastrointestinal carcinoids. Five bronchopulmonary and seven metastatic carcinoids were also examined, for comparison with gastrointestinal carcinoids. The immunohistochemical score (IHS) was calculated from staining intensity and immunoreactive cell population, and ranked according to four grades (negative to strong).
Results:
Cyclo-oxygenase-2 was expressed in all gastrointestinal carcinoids (weak, 1; moderate, 13; strong, 24) and bronchopulmonary carcinoids (weak, 1; moderate, 4), as well as their metastases (moderate, 3; strong, 4). The IHS of COX-2 in larger tumors was significantly lower than that in smaller tumors. However, the IHS of COX-2 at the advancing tumor edge was significantly higher than that at the centers of tumors >or=10 mm in size. Faint COX-1 expression was detected in only one duodenal, one rectal and four bronchopulmonary carcinoids.
Conclusions:
Enhanced COX-2 expression was observed in gastrointestinal as well as bronchopulmonary carcinoids and their metastases, especially at the advancing edges of the tumors. Cyclo-oxygenase-2 may play a role in carcinoid progression.
Insights
Cyclo-oxygenase-2 (COX-2) is highly expressed in carcinoid tumors, particularly at advancing edges, suggesting a role in tumor progression. COX-1 expression was minimal, indicating COX-2 is the primary cyclo-oxygenase involved.
Area of Science:
- Oncology
- Gastroenterology
- Molecular Biology
Background:
- Cyclo-oxygenase-2 (COX-2) is overexpressed in various cancers.
- COX-2 inhibition is explored for cancer prevention and therapy.
- Carcinoid tumors, originating from neuroendocrine cells, show COX-2 expression in normal colorectal mucosa.
Purpose of the Study:
- To investigate the expression of cyclo-oxygenase-1 (COX-1) and cyclo-oxygenase-2 (COX-2) in human gastrointestinal carcinoids.
- To clarify the potential role of COX enzymes in the progression of carcinoid tumors.
Main Methods:
- Immunohistochemical analysis of COX-1 and COX-2 expression in 38 gastrointestinal carcinoids.
- Comparison with 5 bronchopulmonary and 7 metastatic carcinoids.
- Calculation of immunohistochemical score (IHS) based on staining intensity and cell population.
Main Results:
- COX-2 was expressed in all gastrointestinal carcinoids, bronchopulmonary carcinoids, and their metastases.
- COX-2 expression was higher at advancing tumor edges compared to tumor centers in larger tumors.
- Faint COX-1 expression was detected in a limited number of carcinoid samples.
Conclusions:
- Enhanced COX-2 expression is a feature of gastrointestinal and bronchopulmonary carcinoids and their metastases.
- COX-2 is significantly upregulated at the advancing edges of tumors.
- COX-2 likely plays a role in the progression of carcinoid tumors.
