[Effects of cyclooxygenase-2 and proliferating cell nuclear antigen on the onset and development of familial adenomatous polyposis].

BACKGROUND AND OBJECTIVE: Long-term use of cyclooxygenase-2 (COX-2) inhibitors can reduce the incidence of digestive cancers, such as colorectal cancers. Proliferating cell nuclear antigen (PCNA) is an important marker of cellular abnormal proliferation. This study was to evaluate the roles and correlation of COX-2 and PCNA in the onset and development of familial adenomatous polyposis (FAP) diseases. METHODS: Thirty-six specimens of FAP adenomas tissues and 32 specimens of FAP carcinoma tissues from 11 FAP families, and 34 specimens of normal colonic mucosa were collected under colonoscopy from November 2004 to July 2007 in the General Hospital of Beijing Military Command. Immunohistochemistry was used to detect the expressions of COX-2 and PCNA. RESULTS: The positive expression rates of COX-2 in normal colonic mucosa, FAP adenoma, and carcinoma tissues were 0 (0/34), 80.6% (29/36), and 93.8% (30/32), respectively. Proliferation index (PI) in normal mucosa, FAP adenoma, and carcinoma tissues were 17.79+/-7.49, 34.47+/-10.57, and 71.75+/-9.22, respectively. Expressions of COX-2 and PCNA were significantly higher in the FAP adenoma and the carcinoma tissues than in the normal colonic mucosa(P<0.01). The expression of PCNA was significantly higher in the FAP carcinoma tissues than in the FAP adenoma (P<0.01). The expression of PCNA was higher in the FAP adenoma tissues with positive COX-2 than in the FAP adenomas tissues with negative COX-2 (P<0.01). CONCLUSIONS: COX-2 may play an important role in the development of FAP adenomas and colorectal carcinogenesis. COX-2 and PCNA may be important factors in the research on colorectal precancerous lesions and interventional therapy for colorectal neoplasm.

[Expression of cyclooxygenase-2 and relationship with mismatch repair gene and microsatellite instability in hereditary non-polyposis colorectal cancer].

OBJECTIVE: To investigate the expression of Cyclooxygenase (COX)-2 and the relationship between cox-2, mismatch repair gene (MMR) proteins and microsatellite instability (MSI) in HNPCC. METHODS: Twenty-eight cases of adenomas and 14 cases of carcinomas were collected from 33 HNPCC families patients by colonoscopy. Sporadic adenomas (n = 32) and carcinomas (n = 24) were used as a control group. The expressions of COX-2 and mismatch repair gene hMLH1, hMSH2, hMSH6 proteins were examined by immunohistochemistry. MS1 were analyzed by using PCR with BAT25, BAT26, D2S123, D5S346 and D17S250 loci. RESULTS: The COX-2 high-expression rates were 53.6% (15/28) and 42.9% (6/14) in HNPCC adenomas and carcinomas, and were 62.5% (20/32) and 91.7% (22/24) in sporadic adenomas and carcinomas. COX-2 expression was lower in HNPCC carcinomas than that of sporadic carcinomas (P < 0.05). MMR deficiency rate and positive rate of MSI-H were both 71.4% (10/14) respectively in HNPCC carcinomas. It was higher than that in sporadic colorectal carcinomas [both 12.5% (3/24)]. Eight (80.0%) COX-2 low-expression were observed in 10 HNPCC carcinomas with MMR-deficient system while 4 cox-2 high-expression cases were observed in 4 HNPCC carcinomas with MMR-proficient system. COX-2 expression was lower in HNPCC carcinomas and adenomas, sporadic carcinomas with MMR-deficient system than that of MMR-proficient (P < 0.05). The COX-2 low-expression rates were 80.0% (8/10), 66.7% (12/18) and 66.7% (2/3) in HNPCC adenomas, HNPCC carcinomas and sporadic carcinomas with MSI-H. Cox-2 expression was lower in HNPCC and sporadic carcinomas (adenocarcinomas) with MSI-H than that of MSS (P < 0.05). CONCLUSION: Compared with sporadic carcinomas, the COX-2 expression was lower in HNPCC carcinomas. There was negative correlation between COX-2 expression and MMR-deficient (MSI-H). The detection of COX-2, MMR protein and MSI is of important significance in further studying the pathogenesis and interventional therapy of colorectal neoplasms.

[Clinical management of adenomatous polyposis in patients with hereditary non-polyposis colorectal cancer and familial adenomatous polyposis].

OBJECTIVE: To investigate the validity and safety of different doses of non-steroidal anti-inflammatory drugs (NSAID) in attempting to maintain the regression of colorectal adenomas in patients with familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC). METHODS: Twenty-two FAP patients who were willing to receive celecoxib were randomly divided into 2 groups 400 mg/d group (n = 8, taking celecoxib 400 mg/d) and 200 mg/d group (n = 10, taking celecoxib 200 mg/d). Four FAP patients who refused celecoxib and selected aspirin 80 mg/d instead. Six HNPCC patients were given celecoxib 400 mg daily. The treatment lasted for 24 months in all groups. The efficacy was evaluated respectively by the number and grade of polyps by coloscopy every 3 months in the first year and every 6 months in the second year. RESULTS: Either dose of celecoxib could reduce polyps in the FAP patients, with a polyps reduction rate of 86.6% (280/323) in the 400 mg group, significantly higher than that in the 200 mg group [51.81% (129/249) of the aspirin group]. In 5 of the 6 HNPCC patients the polyps completely vanished after 9 months of treatment. Side effects, such as arrhythmia, angina pectoris, and nervous headache, were observed in the celecoxib 400 mg/d group. The side effects could be reversed by decreasing the dose of celecoxib or using aspirin instead. Only one patient in the celecoxib 200 mg/d group showed side effects. CONCLUSION: Celecoxib 400 mg daily is more effective but has more side effects. At first the patients should be treated with celecoxib 200 mg daily for a long time, or 400 mg/d in the first 6 months and then with a daily dose of 200 mg/d to maintain the treatment effects. Soluble aspirin has similar effects.

[Detection of large intragenic mismatch repair genes deletions in Chinese hereditary nonpolyposis colorectal cancer families with multiplex ligation-dependent probe amplification technique].

OBJECTIVE: To gain an insight into the large intragenic hMSH2 and hMLH1 deletions in Chinese hereditary nonpolyposis colorectal cancer (HNPCC) families. METHOD: The large intragenic hMSH2 and hMLH1 deletions in 17 probands of HNPCC families were detected with multiplex ligation-dependent probe Three large intragenic hMSH2 deletions of examplification (MLPA) and GeneMapper techniques. RESULTS: on 8, exon 1-6, and exon 1-7 were found in three families respectively, and no hMLH1 deletion was found. The deletions accounted for 19% of the total hMSH2 and hMLHI germline pathogenic mutations. CONCLUSIONS: The incidence of large intragenic mismatch repair (MMR) genes deletions is relatively higher in Chinese families, and hMSH2 deletions may be more common. It is necessary to detect the large intragenic MMR genes deletions in the molecular detection of HNPCC.