These results clarified rates of lymph node metastasis in SICC according to SM depth, and may contribute to defining therapeutic strategies for SICC.

No abstract

Tubular gland structures of colorectal cancer (CRC) have been demonstrated to undergo dedifferentiation at the primary site, and then the gland structures are re-formed in the liver metastases. In this study, we examined the degree of differentiation of the gland structure of 48 cases of CRCs (24 cases with synchronous liver metastasis, 24 cases without metastasis) by the modified Gleason grading system. We also investigated the role of ZO-1, one of the tight junction proteins, in the morphological changes, i.e., dedifferentiation and redifferentiation, of CRCs at the primary site and liver metastases. Liver-metastasized CRCs (2.47 ± ± ± ±0.37) showed a lower score in the modified Gleason grading system than the corresponding primary tumors (3.28 ± ± ± ±0.36) did, i.e., the tumor cells had undergone redifferentiation at liver metastases. ZO-1 was expressed at the apical cell borders of normal colorectal epithelium, the luminal side of which has tubular gland structures. In comparison with this normal epithelium, the ZO-1 expression level was frequently reduced in primary CRC with liver metastasis (20.8%) and ZO-1 was reexpressed in liver metastasized cancers (79.2%). Furthermore, it was demonstrated by an immunoprecipitation-western blotting analysis on 5 cases of CRC with liver metastasis that ZO-1 bound to epidermal growth factor receptor (EGFR) irrespective of the phosphorylation status of EGFR, and that EGFR associated ZO-1 was highly tyrosine-phosphorylated only in the primary CRC, but was dephosphorylated in the liver-metastasized cancers. Our observations suggest that tyrosine phosphorylation of ZO-1 leads to down-regulation of the function of ZO-1 and dedifferentiation of the glands in CRCs, and these phenomena contribute to liver metastases, and redifferentiation of the glands occurs in the liver metastases. (Cancer Sci 2003; 94: 166-172) ubular gland structures of colorectal cancer (CRC) have been demonstrated to undergo dedifferentiation at the primary site, i.e., the gland structures are broken and the cancer cells, either single or a few cells at a time, invade diffusely into the deepest portion. Subsequently, when the cancer cells reach the liver via the portal vein, the gland structures are re-formed in the liver metastases.1-3) Brablez et al. called this process "redifferentiation" of the CRC cells in the liver metastases, and they also noted that adhesion molecules in the CRC lost their functions at the primary site and then recovered them in the metastases.3) The loss and then recovery of the adhesion molecule function can not be explained by genetic alterations, but appears to be due to transcriptional and/or posttranslational modification. For example, phosphorylation of β-catenin is reported to contribute to such adhesion molecule function. 4,5) Several investigators have reported that dysfunction of the adherens junction was associated with invasion and metastases of various tumors. [6][7][8] However, little information is available concerning the tight junction function in association with...

Background: Surveillance colonoscopy is widely recommended in patients with longstanding and extensive ulcerative colitis (UC) in order to detect colorectal neoplasia at an early stage. However, it still remains questionable whether surveillance colonoscopy effectively enables early detection of UC associated neoplasia. There is a great need for sensitive markers to identify individuals at increased risk of neoplasia. The oestrogen receptor (OR) gene shows age related methylation in the colorectal epithelium and is methylated frequently in sporadic colorectal neoplasia, suggesting that OR methylation may predispose to colorectal neoplasia. Aim: To clarify whether analysis of methylation of the OR gene in non-neoplastic epithelium can contribute to prediction of increased neoplasia risk in UC patients. Materials and methods: A total of 165 non-neoplastic colorectal epithelia from 30 patients with longstanding and extensive UC, including 13 UC patients with neoplasia and 17 patients without, were evaluated. Methylation specific polymerase chain reaction was performed to determine the methylation status of the OR gene. Results: Methylation of the OR gene was detected in 54 of 70 (77.1%) non-neoplastic colorectal epithelia in UC with neoplasia but in only 23 of 95 (24.2%) without neoplasia. Methylation of the OR gene was significantly more frequent in non-neoplastic epithelium from UC with neoplasia than in chronic colitic epithelium from UC without neoplasia. Furthermore, in UC with neoplasia, the OR gene was extensively methylated in non-neoplastic epithelia throughout the colorectum compared with those in UC without neoplasia. Conclusion: These results suggest that analysis of OR gene methylation may have potential as a useful marker for identifying individuals at increased risk of neoplasia among those with longstanding and extensive UC.