Expression of Cyclooxygenase-2 and Its Relationship with Mismatch Repair and Microsatellite Instability in Hereditary Nonpolyposis Colorectal Cancer

• Published in: Chinese medical sciences journal Vol. 25; no. 4; pp. 206 - 210
• Main Authors: Jin, Peng, Sheng, Jian-qiu, Zhang, Ying-hui, Li, Ai-qin, Wu, Zi-tao, Li, Shi-rong
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.12.2010; Department of Gastroenterology,The Military General Hospital of Beijing,Beijing 100700,China
• Subjects: Adult; Aged; Base Pair Mismatch; Base Sequence; colorectal cancer; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics; Cyclooxygenase 2 - genetics; cyclooxygenase-2; DNA Primers; DNA Repair; Female; hereditary nonpolyposis colorectal cancer; Humans; Immunohistochemistry; Male; microsatellite instability; Microsatellite Repeats - genetics; Middle Aged; mismatch repair; 大肠癌; 微卫星不稳定性; 环氧合酶-2; 聚合酶链反应; 肿瘤患者; 遗传性; microsatellite instability; mismatch repair; colorectal cancer; cyclooxygenase-2; hereditary nonpolyposis colorectal cancer
• ISSN: 1001-9294
• DOI: 10.1016/S1001-9294(11)60003-5

Objective To investigate cyclooxygenase-2 （COX-2） expression and its relationship with mismatch repair （MMR） protein expression and microsatellite instability （MSI） in hereditary nonpolyposis colorectal cancer （HNPCC）. Methods A total of 28 cases of colorectal adenoma and 14 cases of colorectal carcinoma were collected between July 2003 and July 2007 from 33 HNPCC families. Sporadic colorectal adenoma （n=32） and carcinoma patients （n=24） served as controls. With samples of tumor tissues and normal colonic mucosa collected from the patients, the protein expressions of COX-2 and MMR （hMLH1, hMSH2, and hMSH6） were examined with immunohistochemical assay. Frequency of MSI in five standard MSI loci BAT25, BAT26, D2S123, D5S346, and D17S250 were analyzed by means of polymerase chain reaction. Results The rate of COX-2 high-expression was 53.6% （15/28） and 42.9% （6/14） in HNPCC adenoma and carcinoma; 62.5% （20/32） and 91.7% （22/24） in sporadic adenoma and carcinoma, respectively. That rate was lower in HNPCC carcinoma than in sporadic carcinoma （P〈0.05）. MMR-deletion rate and percentage of high-frequency MSI （MSI-H） in HNPCC carcinoma were higher than those in sporadic colorectal carcinoma [both 71.4% （10/14） vs. 12.5% （3/24）, both P〈0.01]. Among the 10 MMR-deficient HNPCC carcinoma patients, COX-2 low-expression was observed in 8 cases （80.0%）, while COX-2 high-expression was observed in all of the 4 MMR-positive HNPCC carcinoma cases （P〈0.05）. In comparison to MMR positive HNPCC carcinoma, HNPCC adenoma, and sporadic carcinoma, COX-2 expression was significantly lower in corresponding MMR-deficient cases （all P〈0.05）. The rates of COX-2 low-expression in HNPCC adenoma, HNPCC carcinoma, and sporadic carcinoma with MSI-H were significantly higher than those in the cases with microsatellite stability （all P〈0.05）. Conclusion COX-2 is expressed at a low level in HNPCC carcinoma, different from the high COX-2 expression in sporadic carcinoma.