Microsatellite instability (MSI) has been associated with colitic cancer. However, reported frequency of MSI was varied and the association of MSI with mismatch repair (MMR) deficiency was unclear. In addition, the occurrence of genetic alterations in stromal cells within ulcerative colitis (UC) is still controversial. We therefore sampled 164 microareas in various pathological lesions of UC with or without colitic cancer and studied the MSI status in relation to the DNA repair protein expressions. A total of 129 microfoci from colorectal tissue of 5 colitic cancer patients and 35 microfoci of 7 UC patients (without neoplasm) were carefully sampled by laser-capture microdissection. MSI was analyzed in each microsamples. The protein expression of MMR genes (MLH1, MSH2, MSH6), O 6 -methylguanine-DNA methyltransferase and p53 were assessed by immunohistochemical analysis. Variety of di-nulcleotide microsatellite markers was altered in individual microfoci from different morphological epithelial lesions, in full range of nonneoplastic epithelium to colitic cancer. Interestingly, MSI was not observed in stromal cells at any sites, including those within colitic cancer/dysplasia lesions. Expression of the MMR proteins was not lost in any of the lesions examined. Microsatellite alterations rather seem to be related to the initiation than to the progression of colitic cancer. ' 2006 Wiley-Liss, Inc.Key words: colitic cancer; ulcerative colitis; microsatellite instability; stroma; mismatch repair Colorectal epithelium with a long-standing ulcerative colitis (UC) has an increased risk of developing cancer. 1-6 An invasive colitic cancer often arises from a preceding flat dysplastic epithelium and tend to develop multifocally over the background inflamed epithelium, whilst sporadic colorectal cancer (CRC) develops from a preexisting adenoma, suggesting a dissimilar carcinogenic pathway in colitic cancer. [7][8][9][10][11][12][13][14][15] In lesions undergoing chronic inflammation, microsatellite instability (MSI) is a possible genetic alteration, and high-and low-level of MSI (MSI-H and MSI-L) has been described in UC associated neoplasm (UCAN). [16][17][18][19][20][21][22][23] However, the reported frequency of MSI-H, a consequence of a defective mismatch repair (MMR) system (notably MLH1 or MSH2), and MSI-L, a consequence in part of O 6 -methylguanine-DNA methyltransferase (MGMT) deficiency, 24 has varied considerably from 9 to 50%, and 11 to 85%, respectively. 22,[25][26][27] In situation of considerable genetic heterogeneity within a sample, collection of samples without microdissection could possibly obscure the findings of MSI. 28,29 In fact, analysis of mixed MSI-L components could result in a false diagnosis as MSI-H. To verify true MSI status and to clarify the significance of MSI in colitic carcinogenesis, precise analysis of individual microfoci from various pathological lesions (including stroma) is required. 16,18,19 Accordingly, we sampled 164 microfoci, including nondysplastic epithelium, dysplastic epithel...

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cisplatin (CDDP). Excellent clinical and experimental results have been reported with S-1 for peritoneal dissemination [4], but long-term survival without recurrence is rare, as only a few cases of long-term survival have been reported. Curative surgery is the recommended treatment for gastric cancer. The results of surgery without curability for stage IV patients are generally dismal. It is not known whether or not adjuvant chemotherapy with new anticancer agents such as S-1 is beneficial for the survival of patients with peritoneal dissemination. As curative surgery is considered to be the best therapy for gastric cancer, downstaging with adjuvant chemotherapy and curative surgery is a possibility to improve the prognosis of stage IV gastric cancer patients, after precise preoperative staging.We report the case of a patient with a gastric carcinoma in which peritoneal dissemination disappeared after neoadjuvant chemotherapy with S-1 alone. The patient has survived for over 23 months since the operation, without evidence of recurrence. Case reportA 60-year-old man with anorexia was referred to our hospital, with advanced gastric cancer, detected at an other hospital by upper gastrointestinal endoscopy. Preoperative abdominal computed tomography (CT) scan showed a small amount of ascites and an infiltrative soft-tissue lesion in the peritoneal fat or on the peritoneal surface, suggesting peritoneal dissemination (Fig. 1A). CT also showed lymphadenopathy, which was indicative of metastases, on the lesser curvature of the stomach. Physical examination revealed no specific problems. The serum carcinoembryonic antigen (CEA) level was 1.2 ng/ml and the carbohydrate antigen (CA) 19-9 level was 5.7 U/ml.Gastrointestinal endoscopy revealed that the tumor was located on the greater curvature of the stomach,

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