| The change of APC- -catenin-Tcf/Lef signaling is a very important way in the development of the colorectal carcinoma(CRC). -catenin is a core component of the signaling. -catenin enter into the nuclear to combine with Tcf/Lef when the cytoplasmic level of -catenin is elevated due to the mutation of APC gene, β-catenin gene etc. Then the -catenin-Tcf/Lef complex act as a transcription molecule which resulting in the trascription of genes such as c-myc, cyclin D1, MMP-7, CD44 etc. Finally leading to the malignant transform of the cells. The caveolin may functionally regulate the activation state of caveolae-associated signaling molecules, and have the interaction with APC- -catenin-Tcf/Lef signaling. Recent studies have revealed that caveolin-1 had different expression level in different tumors. There was no reported that the expression of β-catenin and caveolin-1 in CRC is observed simultaneously.With immunohistochemical staining, we examined the expression of -catenin and caveolin-1 in CRC to explore the correlation of -catenin ,caveolin-l and the clinicopathologic parameters, espcially the correlation of -catenin and caveolin-1. In addition, we examined the expression of Ki-67 in order to research the relation between the carcinoma cells proliferation and CRC progress, and the relevance between the carcinoma cells proliferation and the expression of -catenin and caveolin-1.Material and methodsThree hundred fifty four excision specimens of CRC were obtained from the Department of Pathology of Sir Run Run Shaw Hospital from 1994.1 to 2001.12, including 346 cases which contained adjacent nonneoplastic colonic mucosa. Eighty three cases of colonic adenoma, were removed endoscopically or operationally during 1994.1 to 2001.12. Formalin-fixed, paraffin-embedded tissue sections were stained immunohistochemically with anti- -catenin, anti-caveolin-1 and anti-Ki-67 antibodies, with 1:100, 1:400 and 1:50 dilution of primary antibody respectively, positive and negative controls were designed. Immunoreactivity was scored as follows: For β-catenin, if there had membrane staining in more than 90% of cells, the tumor cells were evaluated as normal expression; in cases in which the membrane staining is in less than 90% of cells, or appeared cytoplasmic or nuclear staining, the cancerous tissue was evaluated as abnormal expression. For caveolin-1 and Ki-67: -, no staining to staining in 5% or fewer cells; +, staining in 5% of cells to 25% or fewer cells; 2+, staining in 25% of cells to 50% or fewer cells; 3+, staining in more than 50% of cells. Statistical analysis: statistical significance of differential expression of β-catenin, caveolin-1, and Ki-67 in adjacent nonneoplastic colonic mucosa, adenoma, and CRC, correlation between expression of β-catenin, caveolin-1, Ki-67 and the clinicopathologic parameters of CRC, were analyzed by using the X2 test or Fisher exact test. The univariate survival analysis was based on the life table method, and statistical significance was analyzed by using Wilcoxon(Gehan) test. P values<0.05 were considered significant. Results and discussionThe level of abnormal expression of β-catenin in CRC was obviously higher than that in adenoma and adjacent nonneoplastic colonic mucosa(83.9% vs 42.2% vs 6.6%), the difference was very significant (P<0.005). No statistically significant association was found between 3 -catenin abnormal expression data and sex, age, tumor size, gross type, invasive depth, lymph node status, Dukes' stage, but the β-catenin abnormal expression was positive correlated with histiologic type of CRC. The level of abnormal expression of β-catenin of moderately or poorly differentiated tubular adenocarcinoma and mucinous adenocarcinoma was higher than that of well differentiated tubular adenocarcinoma, had astatistically significant association (P<0.05). This results indicated that -catenin abnormal expression plays an important role in the development of CRC, and have no association with the invasive activity of CRC. It i... |
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