| Colorectal carcinoma (CRC) is one of the most common malignancies in digestive tracts. Although comprehensive therapies have been used, the prognosis of CRC is still poor, which is possibly due to the lack of early effective diagnosis and effective targets of anti-metastasis. Therefore, further exploring the alterations of key genes related to development and progression of CRC will be considered useful. Recent studys have indicated that beta-catenin is a multifunctional protein, which not only mediates cell-cell adhesion of the same types by combining to E-cadherin, but acts as the key factor of APC-beta-catenin-Tcf4/Lef signal transduction pathway. The abnormal expression of beta-catenin is possibly involved in the development and progression of CRC. Degradating almost all components of extracellular matrix, matrix metalloproteinase-7 (MMP-7) is hence considered to be related to invasion/metastasis of malignancies. Studies in vitro have indicated that MMP-7 is one of the likely target genes of beta-catenin-Tcf4/Lef pathway and that synergistic action of beta-catenin and MMP-7 may play an important role in the carcinogenesis and invasion/metastasis of CRC. Progression tissue microarrays of CRC, which contain samples from normal mucosae, kinds of adenomas, malignant changes in adenoma and kinds of adenocarcinomas, have been applied to high throughputly study molecular alterations in the different stages of CRC. To our knowledge, seldom have the investigations on significance of synergistic expression of beta-catenin and MMP-7 in CRC and adenomas been made overseas, and none of such ever done in China. The specific role and mechanism of oncogenic beta-catenin enhancing MMP-7 expression on carcinogenesis and invasion/metastasis of CRC remains unclear. In order to investigate the impact of synergistic expression of beta-catenin and MMP-7 on development and progression of CRC, we first constructed the Progression tissue microarrays of CRC in the current study, and then detected beta-catenin and MMP-7 protein expressions by immunohistochestry. finally the mRNA expression levels of beta-catenin and MMP-7 were examined using in situ hybridization in the tissue microarrays, The main results and conclusions are as follows:1. The nuclear beta-catenin abnormal expression rate of malignant changes in adenoma was significantly higher than that of the normal colorectal mucosae, adenoma and carcinoma, which indicated that oncogenic activation of beta-catenin were closely related to the malignant transformation of colorectal adenoma. The cytoplasmic/nuclear beta-catenin abnormal expression rates of high-grade intra-epithelial neoplasia were considerably higher than that of low-grade, which showed that the cytoplasmic and nuclear accumulation of beta-catenin were likely early events in carcinogenesis of CRC.2. In adenocarcinoma tissue, the nuclear beta-catenin abnormal expression rates of adenocarcinoma with positive lymph node metastasis, C and D stages were all significantly higher than that of negative lymph node, A and B stages, which indicated that oncogenic activation of beta-catenin was in high correlation with invasion/metastasis of CRC and may be regarded as a useful marker for the prediction of metastasis.3. Both mRNA and protein positive expression rates of MMP-7 in malignant changes in adenoma and adenocarcinoma were significantly higher than that of normal mucosa tissue. Furthermore, the mRNA and protein positive expression rates of MMP-7 in adenocarcinoma were all closely related to lymph node metastasis status and Dukes stages. These results indicated that overexpression of MMP-7 not only facilitated CRC to invasively grow, but was possibly related to carcinogenesis of CRC. 4. The nuclear beta-catenin abnormal expression was in positive correlation with the positive expressions of mRNA and protein of MMP-7, and a pair of serial sections was carried out showing that concordance of between nuclear accumulation of beta-catenin and cytoplasmic overexpression of MMP-7 were observed in adenoma, malignant ch...
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