Study on genetic instability of nm23-H1 gene and expression of hMLH1, hMSH2 in sporadic gallbladder carcinoma / 中国病理生理杂志

ABSTRACT

AIM: To examine the MSI and LOH of locus D17S396 and their influence on the expression of nm23-H1 in gallbladder tumors, and to examine the protein expression of hMLH1/hMSH2, which may provide experimental evidence for the tumor occurrence and metastasis. METHODS: Techniques such as DNA extraction, CR-SSCP, ordinary silver stain were used to study MSI and LOH of locus D17S396. Envision IHC was used to assess the expression of nm23-H1 and hMLH1/hMSH2.RESULTS: ① The frequency of heredity instability of gallbladder carcinoma was 42.55%. The frequency of LOH in liver and lymph node metastasis cases and in stage Nevin IV and V was significantly higher than that without metastasis and stage I, II and III. However, the frequency of MSI showed contrary correlation with some clinicopathologic characteristics. ② The expression of nm23-H1 was 46.81%. The case with lymph node metastasis and Nevin stage IV and V showed significantly lower expression than that without lymph node metastasis and stage I, II and III. ③ The expressions of hMLH1 and hMSH2 were 51.06% and 42.55% respectively. hMLH1 in lymph node and liver metastasis cases and in stage Nevin IV and V were significantly lower than that without metastasis and in stage I, II and III. ④ Positive frequency of hMLH1 in MSI positive group was higher than that in MSI negative group. The positive frequency of nm23-H1 and hMSH2 protein in LOH positive group was lower than that in negative group.CONCLUSION: The heredity instability of nm23-H1 gene may be implicated pathogenesis and progression of gallbladder carcinoma. Both MSI and LOH of nm23-H1 control the development of gallbladder carcinoma independently in different paths. Abnormal expression of hMLH1/hMSH2 may be a molecule marker in early stage of gallbladder carcinoma.