BACKGROUND Tumor budding is present in the stroma at the invasive margin of colorectal carcinomas (CRC). The disintegration of cell adhesion molecules is closely related to this process. This study investigated the role of tumor budding in the progression of CRC, and compared the expression of beta-catenin and E-cadherin between tumor budding and tumor center to determine whether epithelial-to-mesenchymal transitions (EMTs) occur in tumor budding. METHODS: The number of tumor budding (NTB) instances was determined in 58 cases of CRC, and immunoreactivities of E-cadherin and beta-catenin were compared at the tumor center and at the tumor budding site.
Immunohistochemical staining for vimentin was also done. RESULTS Tumor budding was seen in 52 tumors (90%). There were significant associations between NTB and cliniopathologic parameters such as tumor depth, nodal metastasis and clinical stage.
Expression of cytoplasmic and nuclear beta-catenin were significantly higher at tumor budding sites than in the tumor center. In contrast, expression of membranous and cytoplasmic E-cadherin were significantly higher in the tumor center than at the tumor budding sites. Vimentin was expressed at tumor budding foci of only 2 cases (3%). CONCLUSIONS This study suggests that EMT occurs at tumor budding, and that NTB may be a good marker for predicting a poor prognosis in CRC.
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The E-cadherin, alpha-catenin, and beta-catenin expressions were immunohistochemically investigated in paraffin-embedded materials of 80 cases of colorectal adenocarcinomas. The staining similar to normal colorectal mucosa with preserved strong membranous staining pattern was considered normal or preserved expression. The X2 test was used to analyse the statistical correlation of cadherin/catenin expression with clinicopathologic parameters and the Breslow test for the correlation with survival length. Normal colorectal mucosa showed strong membranous expression of cadherin/catenin complex. The reduced E-cadherin, alpha-catenin, and beta-catenin expression were found in 53/80 (66.3%), 46/80 (57.5%), and 44/80 (55.5%) cases of colorectal cancers examined, respectively. There were significant correlations between E- cadherin and alpha -catenin (p=0.035), and between alpha-catenin and beta-catenin (p=0.013). The reduced E-cadherin expression was associated with histologic dedifferentiation, tumor depth, lymph node metastasis, clinical stage (p<0.05), poor clinical outcome in stage II (p=0.016) and the reduced alpha-catenin expression with lymph node metastasis and clinical stage (p<0.05). Reduced expression of two or more proteins was correlated with lymph node matastasis, histologic dedifferentiation, clinical stage, and survival (p<0.05). The present study demonstrates a significant down-regulation of E-cadherin and alpha-catenin expression in colorectal cancer is associated with tumor invasiveness, histologic dedifferentiation, lymph node metastasis, and clinical stage. These results suggest that E-cadherin and alpha-catenin may be useful markers of invasiveness, lymph node metastatic potential, and clinical stage and of value as prognostic markers in the earlier stage. Further studies are needed to confirm the prognostic value of these cadherin/catenin complex.
BACKGROUND Gastric cancer is reported to be one of the leading causes of mortality in Korea. Our aim was to evaluate the clinicopathologic usefulness of cyclin E, p53, E-cadherin and beta-catenin expressions in gastric adenocarcinomas. METHODS Immunohistochemical staining was performed on the 40 early gastric carcinoma (EGC) cases and 69 advanced gastric carcinoma (AGC) cases to examine the relationship with the clinicopathologic parameters. RESULTS Cyclin E and p53 expressions were significantly lower in the mucosal or submucosal invasion group compared with those in the muscle invasion and subserosal or serosal invasion groups. Cyclin E expression was significantly higher in the node-positive group compared with that in the node-negative group. The loss of beta-catenin expression was significantly higher in the node-negative group. p53 expression was significantly higher in the intestinal type group than that in the diffuse type group. Loss of E-cadherin expression was significantly higher in the diffuse type group. Cyclin E expression correlates with p53 expression. CONCLUSIONS The depth of invasion seems to correlate with cyclin E and p53 expressions. Lymph node metastasis may correlate with loss of beta-catenin expression.