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15000 Background: A tight junction is one of components of intercellular junctional complexes and play an important role in maintaining barrier function and cellular porlarity. Claudin, occluding, and ZO-1 are known as trans-membrane proteins which compose tight junction. Roles of these tight junction-associated proteins of gastric cancer is not yet determined. In this study, we investigated expression levels of these proteins in gastric cancer immunohistochemically and compared the results with clinicopathological features of the tumors and patient prognosis. Methods: One hundred and twenty-four gastric cancer patients underwent gastrectomy between 2000 and 2004 were included in this study. Formalin fixed and parafine embedded tissues were sliced into 4-μm sections and immunohistchemistry was performed using anti-claudin-4, anti-occluding and anti-ZO-1 antibodies. Stained slides were investigated and the incidence of positive cells was graded as: 0, negative; 1, < 20 %; 2, 20–80 %; 3, >80 %. Results: The expression of claudin-4, occludin, and ZO-1 was observed at the membrane, and the positivity rates in cancer tissues were 87.1%, 95.2% and 100%, respectively. In concerning with correlation between protein expression and clinicopathologic features, claudin-4 expression was significantly decreased in tumors with undifferentiated type adenocarcinoma (p No significant financial relationships to disclose.

13034 Background: We have previously reported that tumors with high orotate phosphoribosil transferase (OPRT) and low dihydropyrimidine dehydrogenase (DPD) mRNA expression levels showed remarkable sensitivity to 5-fluorouracil (5-FU) by real-time RT-PCR using fresh frozen (FF) tumor samples. However, the use of fresh frozen samples has some limitations. The use of formalin fixed parafine embedded (FFPE) samples has great advantage to apply these technologies for clinical settings. In order to investigate the feasibility of real-time RT-PCR from FFPE samples to predict sensitivitiy to 5-fluorouracil (5-FU), we investigated the gene expression levels of 5-FU metabolism-relating enzymes by real-time RT-PCR from FFPE samples and compared the results from FF samples in gastric and colorectal cancer. Methods: FFPE samples and FF samples were obtained from 46 patients with gastric cancer and 29 patients with colorectal cancer. Gene expression levels of tymidylate synthase (TS), OPRT, thymidine phosphorylase (TP) and DPD were determined by quantitative real-time RT-PCR. In FFPE samples tumor tissue was obtained using laser captured microdissection (LCM). Tumor sensitivity to 5-FU was evaluated by in vitro ATP assay. Results: Gene expression levels of TS, TP, DPD determined from FFPE samples significantly correlated with those from FF samples. Although respective gene expression levels alone failed to show signifcianct correlation with the in vitro 5-FU sensitivity, statistically significant correlation was noted either from the samples of FF or FFPE in both gastric (FF: r = 0.660, FFPE: r = 0.780) and colorectal cancer (FF: r = 0.780, FFPE: r = 0.660), when OPRT/DPD mRNA ratio was applied for comparison with the results of 5-FU sensitivity. Thus, high OPRT/DPD ratio determined from FFPE samples resulted in high sensitivity to 5-FU. Conclusions: From these results, it is suggested that sensitivity to 5-FU is predictable by quantitative RT-PCR using FFPE samples. Measurement of 5-FU metabolism-relating enzyme gene expression level from FFPE samples appeared to be feasible for predicting 5-FU sensitivity and to have great advantage to apply the molecular predicting assay in clinical settings. [Table: see text]

4143 Background: Five-fluorouracil (5-FU) is still one of the key-drug for chemotherapy in gastric and colorectal cancer. Therefore, prediction of 5-FU sensitivity is of great importance for chemot...

4200 Background: We had previously reported that peritoneal micrometastasis determined by CEA mRNA level in peritoneal washings using real-time quantitative RT-PCR (RQ-PCR) is a good predictor for ...