Expression of cyclooxygenase-2 and its relationship with mismatch repair and microsatellite instability in hereditary nonpolyposis colorectal cancer.

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 (Pü0.05). 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 Pü0.01]. 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 (Pü0.05). In comparison to MMR positive HNPCC carcinoma, HNPCC adenoma, and sporadic carcinoma, COX-2 expression was significantly lower in corresponding MMR-deficient cases (all Pü0.05). 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 Pü0.05). CONCLUSION: COX-2 is expressed at a low level in HNPCC carcinoma, different from the high COX-2 expression in sporadic carcinoma.

Clinicopathological features of non-familial colorectal cancer with high-frequency microsatellite instability.

OBJECTIVE: To explore the clinicopathological features of non-familial colorectal cancer with high-frequency microsatellite instability (MSI-H). METHODS: One hundred and fifty patients with colorectal cancer who had no family history were enrolled in this study from June 2006 to June 2008. Five standard microsatellite loci including BAT25, BAT26, D2S123, D5S346, and D17S250 were amplified with immunofluorescent polymerase chain reaction. The patient information including age, sex, and tumor location was recorded. Pathological features including differentiation, mucinous differentiation, histological heterogeneity, and Crohn's-like reaction were observed under light microscope. The presence of tumor-infiltrating lymphocytes (TLs, CD4+ and CD8+) was detected by means of immunohistochemistry. A regression equation was obtained by stepwise logistic regression analysis to evaluate the relationship between MSI-H phenotype in colorectal cancer and pathological features. RESULTS: MSI-H phenotype occurred in 13.33% of the 150 patients with non-familial colorectal cancer. Poor differentiation, histological heterogeneity, Crohn's-like reaction, and presence of TLs were found to be independent factors to identify MSI-H non-familial colorectal cancer. Logistic regression equation showed an overall sensitivity of 70.0%, specificity of 99.2%, and accuracy of 95.3% in identifying MSI-H non-familial colorectal cancer. CONCLUSION: MSI-H non-familial colorectal cancer manifests specific pathological features, which may be relied upon for effective identification of that disease.

[Application of ICP-AES to detecting nutrients in grain of wheat core collection of China].

Deficiency of micronutrients, especially iron and zinc, has been a serious malnutrition problem worldwide in human health. Increasing Fe and Zn concentrations in grains by means of plant breeding is a sustainable, effective and important way to improve human mineral nutrition and health. However, little information on grain Fe and Zn concentrations in Chinese wheat genotypes is available. Therefore, to determine the nutrients status especially these of micronutrients in wheat grain is necessary and very useful. Two hundred sixty two genotypes were selected from the wheat mini-core collections, which contained 23090 wheat genotypes in China and represented 72.2% of total genetic variation. All 262 genotypes were grown in soils of similar geographical and climate location in order to minimize the environmental effect. After harvesting, the grains were washed with deionized water and dried (around 70 degrees C), then digested in HNO3 solution using a microwave accelerating reaction system (MARS). Nutrient concentrations in stock solution were analyzed by inductively coupled plasma atomic emission spectrometry (ICP-AES). Remarkable genetic variations among grain nutrient concentrations (Fe, Mn, Cu, Zn, Mg, Ca, K and P ) in the tested genotypes were detected. The concentrations of Fe, Zn, Mn, Cu, Ca, Mg, K and P in wheat grain were in the ranges of 34.2-61.2, 26.3-76.0, 20.9-56.7, 3.4-9.8, 290-976, 1129-2210 mg x kg(-1); 0.34%-0.85% and 0.296%-0.580%, respectively. The corresponding average values were 45.1, 50.2, 37.9, 6.5, 515, 1772 mg x kg(-1), 0.55% and 0.451%, respectively. Significant positive correlations between micronutrients (Fe, Mn, Zn, and Cu) in wheat grains were detected, and the correlation coefficients were 0.395** (Fe and Mn), 0.424** (Fe and Zn), 0.574** (Fe and Cu), and 0.474** (Mn and Cu), respectively. However, no significant difference was found in grain nutrient concentrations between spring-wheat and winter-wheat genotypes. This study provides valuable and important information for breeding wheat genotypes which are enriched with minerals in grains, especially Fe and Zn