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.