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Background/aims: Recently, it has been reported that HACE1, the E3 ubiquitin ligase, is epigenetically inactivated in human Wilms' tumors and HACE 1 expression was also down-regulated in colorectal and gastric carcinomas., Methodology: In this study, methylation status of the HACE1 gene was examined in primary carcinomas and the corresponding normal tissues derived from 27 patients with HCC using quantitative methylation-specific PCR (qMSP)., Results: Methylation of the HACE1 gene was detected in 18 out of the 27 (67%) HCCs, suggesting that the methylation of HACE1 was frequently observed in HCC. The clinicopathological data were then correlated with these results. In the value of serum AFP (α-fetoprotein), a significant difference was observed (p=0.0025)., Conclusions: All stages of HCCs presented HACE1 methylation, indicating that the HACE1 gene has been methylated from the early stages of HCCs.

Background: Predictors of the response of colorectal cancer to chemotherapy remain poorly understood. We analyzed the mRNA expression levels of enzymes related to sensitivity to 5-fluorouracil derivatives in patients with colorectal cancer., Patients and Methods: Danenberg tumor profile method (DTP) was used in order to measure mRNA expression levels of thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD), and thymidine phosphorylase (TYMP) from 180 patients with colorectal cancer. The relations of expression levels with clinicopathological factors and outcomes were studied., Results: Higher TYMS expression was associated with greater age, DPYD expression with greater age, poorer differentiation and low invasion, and TYMP expression with poorer differentiation and lack of peritoneal metastasis. DPYD expression positively correlated with TYMP expression. In patients with stage IV disease, high DPYD or TYMP expression was associated with poor outcomes., Conclusion: mRNA expression of TYMS, DPYD, and TYMP is associated with distinct characteristics and may be useful for predicting survival in patients with stage IV colorectal cancer.

Background: Recently, the human deafness, autosomal dominant 5 gene, DFNA5, has frequently been detected in cancer tissues. The methylation status of the DFNA5 gene in colorectal cancer was examined and was compared to the clinocopathological findings., Materials and Methods: Eighty-five tumor samples and corresponding normal tissues were obtained from patients with colorectal cancer who underwent surgery at our hospital. The methylation status of the DFNA5 gene in these samples was examined by quantitative methylation-specific PCR (qMSP). Subsequently, the clinicopathological findings were correlated with the methylation status of the DFNA5 gene., Results: DFNA5 gene methylation was found in 29 (34%) out of the 85 colorectal carcinomas, suggesting that it was frequently observed in colorectal cancer. A significant correlation with methylation was observed for lymphatic vessel invasion and TNM stage (p=0.0268 and p=0.0189, respectively)., Conclusion: DFNA5 might act as a tumor suppressor gene and DFNA5 gene methylation might play an important role in the development of colorectal cancer. Our data implicate DFNA5 gene methylation as a novel molecular biomarker in colorectal cancer.

Aim: Detection of gastric cancer using serum assay of vimentin methylation., Methods: A quantitative methylation-specific polymerase chain reaction assay was used to detect vimentin gene (VIM) methylation in the serum of 71 patients with gastric cancer., Results: Mean VIM methylation in cancer patients (0.304 ± 0.558) was significantly higher than that in healthy donors (0.011 ± 0.015, p=0.018). The sensitivity of VIM methylation (33.8%) was similar to the one of carbohydrate antigen 19-9 (CA19-9) (25.4%), higher than the one of carcinoembryonic antigen (CEA) (12.7%), and significantly higher than the sensitivity of both markers for patients with stage I and IV disease (p=0.010 and 0.044, respectively). At all stages, the sensitivity of a combination of markers was higher than the sensitivity of any in isolation marker and was similar for stages I, II and III, reaching 76.9% for stage IV disease., Conclusion: VIM methylation may represent a useful marker for the detection of tumor DNA in the serum of patients with gastric cancer.

Background: Homeodomein only protein x (HOPX) gene methylation has frequently been detected in cancer tissues. The methylation status of the HOPX gene in colorectal cancer was examined and compared to the clinocopathological findings., Materials and Methods: Eighty-nine tumor samples and corresponding normal tissues were obtained from colorectal cancer patients who underwent surgery at our hospital. The methylation status of the HOPX gene in these samples was examined by quantitative methylation-specific PCR (qMSP). Subsequently, the clinicopathological findings were correlated with the methylation status of the HOPX gene., Results: HOPX gene methylation was found in 46 (52%) out of the 89 colorectal carcinomas, suggesting that it was frequently observed in colorectal cancer. A significant increase of methylation was observed in the poorly differentiated carcinomas (p=0.0049)., Conclusion: HOPX gene methylation could play an important role for the development of colorectal cancer and is closely related to the histological type.

A 55-year-old woman was found to have a type-4 lesion centered on the greater curvature of the lower portion of her stomach during an upper gastrointestinal endoscopic examination.A diagnosis of inoperable advanced gastric carcinoma [type 4, tub 2/por, T3 (SE), N3, H0, P1, cStage IV], complicated by pyloric stenosis, liver dysfunction, and obstructive jaundice untreatable by bile drainage, was made.After obtaining the informed consent of the patient and her family and explain- ing that under the circumstances surgery was not indicated, chemotherapy [S-1 (granules) 80 mg/m2, CDDP 60 mg/m2] was selected. After starting treatment, an improvement in liver dysfunction and jaundice was observed, and at the start of the second course, the patient had become capable of oral feeding.The patient was discharged after completion of the second course. No choices associated with evidence exist for treatment of patients with inoperable advanced gastric cancer (complicated by obstructive jaundice), who are not elderly and have good performance status (PS).We report this case in which improvement of activity of daily living (ADL) was achieved relatively safely by treatment with S-1/CDDP, together with a brief discussion based on the literature.

Background: Recently, metastasis associated with colon cancer 1 (MACC1) gene was identified by genome-wide search for differentially expressed genes in human colon cancer tissues and metastases. Previously, MACC1 expression was examined in colorectal carcinomas and gastric carcinomas and was found to show significant correlation with peritoneal dissemination., Patients and Methods: In this study, MACC1 expression was analyzed in 60 samples (tumor and the surrounding non-tumorous liver tissue) collected from 30 patients with hepatocellular carcinoma (HCC) using quantitative real-time polymerase chain reaction (QRT-PCR). Results. MACC1 expression score (tumor:normal) in primary HCC was between 0.01 and 4.59 (average±SD=0.68±0.94). Subsequently, clinicopathological data were correlated with the MACC1 expression. It was found that MACC1 expression showed significant correlation with vascular invasion and α-fetoprotein level (p=0.034, p=0.0098, respectively)., Conclusion: These results suggest that MACC1 is more frequently expressed in vascular invasive HCC and may serve as a new parameter for the prognostic prediction of HCC.

Background: Recently, it has been shown that the loss of the human histone acetyl transferase, TIP60, led to an accumulation of double-strand DNA breaks and has been linked to a growing number of cancer types., Materials and Methods: TIP60 expression levels were examined in 46 gastric cancer samples using a quantitative real-time polymerase chain reaction (QRT-PCR). Subsequently, clinicopathological data were correlated with the TIP60 expression score., Results: A down-regulation of the TIP60 gene was observed in 28 out of 46 (61%) specimens of primary gastric cancer. TIP60 down-regulation showed significant correlation with patient age (p=0.0224), depth of tumor invasion (p=0.0401) and lymph node metastasis (p=0.0481)., Conclusion: The down-regulation of TIP60 is important for the malignant pathway of gastric carcinogenesis.

Background: Recently, metastasis associated with the colon cancer 1 (MACC1) gene was identified by genome-wide search for differentially expressed genes in human colon cancer tissues and metastases. Previously, the MACC1 expression levels were examined in colorectal carcinomas and it was found that MACC1 expression showed significant correlation with peritoneal dissemination and higher stage of TNM classification., Materials and Methods: In this study, MACC1 expression levels were analysed in 41 gastric cancer samples using quantitative real-time polymerase chain reaction (QRT-PCR). Results. Distribution of MACC1 expression scores in primary gastric carcinomas was between 0.01 and 4.36 (average ± SD was 1.34 ± 1.31). Subsequently, clinicopathological data were correlated with the MACC1 expression. It was found that MACC1 expression showed significant correlation with peritoneal dissemination (p=0.038)., Conclusion: These results suggest that MACC1 is more frequently expressed in peritoneal-disseminated gastric carcinomas and may serve as a new parameter for the prognostic prediction of gastric cancer.

Background: A tumor suppressor gene, p16, was found to harbor promoter methylation associated with the loss of protein expression in cancer cells, suggesting that p16 inactivation due to promoter methylation may be important for gastric tumorigenesis., Patients and Methods: The methylation status of the p16 gene was examined in primary carcinomas and the corresponding normal tissues derived from 49 patients with gastric cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: Aberrant methylation of the p16 gene was detected in 17 out of the 49 (34%) primary gastric carcinomas, suggesting that the aberrant methylation of p16 is frequently observed in gastric carcinomas. The clinicopathological data were then correlated with these results. Significant differences were observed with lymphatic invasion (p=0.046) and tumor site (p=0.010)., Conclusion: p16 might act as a tumor suppressor in gastric carcinomas and appears to be more frequently methylated in lymphatic-invasive gastric carcinomas.

Background: Recently, Stein et al. identified the metastasis-associated in colon cancer 1 (MACC1) gene by genome-wide search for differentially expressed genes in human colon cancer tissues and metastases., Patients and Methods: We analyzed MACC1 expression levels in 52 colorectal cancer samples using quantitative real-time polymerase chain reaction (QRT-PCR)., Results: We found that MACC1 expression showed significant correlation with peritoneal dissemination (p=0.042) and higher stage of TNM classification (p=0.007)., Conclusion: These results suggest that MACC1 is more frequently expressed in advanced colorectal carcinomas.

Background: Recently, it has been reported that TFPI2 (tissue factor pathway inhibitor-2), a Kunitz-type serine proteinase inhibitor, is frequently methylated in human colorectal cancer using a gene expression array-based strategy. The aim of this study therefore was to examine whether the TFPI2 methylation in surgically removed colorectal cancers was correlated to the clinicopathological features., Materials and Methods: The methylation status of the TFPI2 gene was examined in primary carcinomas and corresponding normal tissues derived from 50 patients with colorectal cancer using quantitative methylation-specific PCR (qMSP), and the correlation between the methylation status and the clinicopathological findings was evaluated. Results. Methylation of the TFPI2 gene was detected in 31 out of the 50 (62%) primary colon carcinomas, suggesting that the methylation of TFPI2 is frequently observed in colorectal cancer. The clinicopathological data were compared with these results. Significant differences were observed between methylation of TFPI2 and histology (p=0.0053) or lymph node metastasis (p=0.0396). These results indicated that TFPI2 was more frequently methylated in well-differentiated advanced colorectal carcinomas., Conclusion: TFPI2 may act as a tumour suppressor in colorectal carcinomas and TFPI2 methylation may present a potential risk of malignancy in colorectal cancer.

Background: Recently, Herfarth et al. reported that a subset of colorectal tumors was characterized by a specific methylation pattern in the MGMT promoter associated with reduced MGMT expression., Materials and Methods: Methylation status of the MGMT gene was examined in primary carcinomas and the corresponding normal tissues derived from 38 patients with gastric cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: Aberrant methylation of the MGMT gene was detected in 4 out of the 38 (11%) primary gastric carcinomas, suggesting that the methylation of MGMT is observed in gastric carcinomas as well as colorectal ones. The clinicopathological data were correlated with the methylation results. A significant difference was observed in the extent of tumor (p=0.0470), lymph node metastasis (p=0.0470), and TNM stage (p=0.0377) (Table I). Moreover, a trend was shown toward large maximal tumor size in methylated tumors (p=0.134)., Conclusion: MGMT was more frequently methylated in advanced gastric carcinomas.