Expressions Of HMSH2, HMLH1, TβRⅡ, E-cadherin, β-catenin, MMP-7, TIMP-2 And Their Correlation To The Invasion/metastasis Of Hereditary Nonpolyposis Colorectal Cancer

ObjectiveHereditary nonpolyposis colorectal cancer (HNPCC) is an important subgroup of colorectal carcinomas. Compare to sporadic colorectal cancer(sporadic CRC), HNPCC present several particular features, the most important of which are less invasive and metastatic properties linked to a more favorable prognosis.The aim of our study is to investigate the correlation of hMSH2, hMLH1, transforming growth factorβreceptor typeⅡ(TβRⅡ), E-cadherin (E-cad), P-catenin (β-cat), matrix metalloproteinase-7(MMP-7) and tissue inhibitor of metalloproteinase-2 (TIMP-2) expression with biological behaviours of HNPCC.MethodsThe expressions of hMSH2, hMLH1, TβRⅡ, E-cad,β-cat, MMP-7 and TIMP-2 protein were detected by immunohistochemical staining in tumors tissue including 30 cases of sporadic CRC, 30 cases of HNPCC and 8 cases of normal colorectal mucous membrane. And their clinical data were studied retrospectively.ResultsThe positive expression rates of hMSH2, hMLH1, TβRⅡ, E-cad,β-cat, MMP-7 and TIMP-2 were significantly related to the depth of invasion and lymph node metastasis, but not to the sex and the size or position of the tumour. The discrepancy of positive expression rate of hMSH2,hMLH1,TβRⅡ,E-cad,β-cat,MMP-7 and TIMP-2 were remarkable between in sporadic CRC and in HNPCC. The expression of hMSH2 had a positive correlation with hMLH1 in HNPCC and sporadic CRC. The expression of TβRⅡhad a positive correlation with hMSH2, hMLH1 and MMP-7, and negative correlation with TIMP-2. The expression of MMP-7 had a negative correlation with TIMP-2 in HNPCC and sporadic CRC. The expression of E-cad positively correlated withβ-cat in membrance. However, the expression ofβ-cat in membrance negatively correlated withβ-cat in plasma, and the expression ofβ-cat in plasma positively correlated with MMP-7.ConclusionThe mutation of mismatch repair gene(MMR),mainly hMSH2 and hMLH1, also beget the mutational inactivation of TβRⅡwhile they cause HNPCC. So HNPCC tumors can escape the inhibition of TGFβ1. However TGFβ1 can induce the expression of MMP-7 and down-regulate the expression of TIMP-2 in tumors via E-cad andβ-cat. This might be one reason of special biological behaviours of HNPCC.