q-Space MR imaging ex vivo provides excellent diagnostic accuracy for evaluating mural invasion by esophageal carcinomas, the histologic grades of esophageal carcinomas, and lymph node metastasis by esophageal carcinomas.

Diffusion-tensor MR imaging and tractography are feasible in esophageal specimens and provide excellent morphologic data for the evaluation of mural invasion by esophageal carcinomas.

Mlh1-knockout mice have been developed as a useful model of hereditary non-polyposis colorectal cancer (HNPCC). In this study, we analyzed the pathology of gastrointestinal tumours (GIT) in these mice in detail and examined the possible effects of ionizing radiation on the induction of intestinal tumours to evaluate the late response to radiotherapy in HNPCC. Mlh1-/- mice spontaneously developed GIT and thymic lymphomas by 48 weeks. GIT included not only well differentiated adenocarcinomas but also poorly differentiated and mucinous adenocarcinomas, suggesting that this mouse is a good model for HNPCC. In contrast to colon cancers from HNPCC patients, however, carcinomas of Mlh1-/- mice expressed p53 and showed a lack of transforming growth factor (TGF)-betaRII mutation, which resulted in the expression of TGF-betaRII protein. Irradiation of 10-week-old Mlh1-/- mice accelerated GIT development but had little effect at 2 weeks. Mlh1+/- and Mlh1+/+ mice were not susceptible to spontaneous or radiation-induced thymic lymphomas and GIT until 72 weeks after birth. The development and pathology of GIT in Mlh1-/- mice suggest that this mouse is a good model for HNPCC, although tumour-related responsible genes might be different from HNPCC. As X-ray exposure promoted carcinogenesis of GIT in adult Mlh1-/- mice, an increased risk of secondary cancers after radiotherapy for HNPCC patients should be taken into consideration.

Objective: Inflammatory bowel disease, which frequently accompanies silencing of Mlh1, plays a key role in the pathogenesis of colorectal cancer. The interaction between inflammation and mismatch repair deficiency, however, remains unclear. The aim of this study was to determine the effect of inflammation on colorectal carcinogenesis in Mlh1-deficient mice. Method: Inflammatory colitis was induced by treatment with 1% dextran sodium sulfate (DSS) in drinking water for 1 week in Mlh1 knockout (Mlh1^–/–), Mlh1 heterozygous (Mlh1^+/–) and wild-type (Mlh1^+/+) mice at 10 weeks of age. The development of colon tumors was followed for a subsequent 15 weeks and the tumors were analyzed immunohistochemically for the expression and localization of iNOS, β-catenin and p53. Results: Male and female Mlh1^–/– mice with DSS showed a 63 and 44% incidence of tumors, respectively, whereas no tumors were observed in Mlh1^+/– and Mlh1^+/+ mice. The mice without DSS treatment did not develop any tumors regardless of the genotype. While aberrant expression of β-catenin was not detected in colonic neoplasms, p53 and iNOS expression was increased in 100 and 77%, respectively. These immunohistochemical changes were consistent with those of human colon cancers associated with ulcerative colitis. Conclusion: Our results indicate that Mlh1 deficiency strongly accelerates colon carcinogenesis when combined with inflammation. Thus the cells with Mlh1 deficiency, either inherently or colitis associated, may be at an increased risk of cancer under inflammatory conditions.

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