Methylation of the WNT5A gene is frequently detected in early gastric carcinoma.

BACKGROUND/AIMS: Recently, it has been reported that WNT5A methylation was frequently detected in colorectal cancers. However, the relationship between the WNT5A methylation and the characteristics of gastric cancer remains unknown. METHODOLOGY: Methylation status of the WNT5A 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 WNT5A gene was detected in 7 out of the 38 (18%) primary gastric carcinomas, suggesting that the methylation of WNT5A 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=0.0226). Moreover, a trend was shown towards early TNM stages in methylated tumors (p=0.209). CONCLUSIONS: WNT5A was more frequently methylated in early gastric carcinomas.

Methylation of the TFPI2 gene is frequently detected in advanced gastric carcinoma.

BACKGROUND: Recently, Glockner et al. identified the methylation of TFPI2 as a frequent event in human colorectal cancer using a gene expression array-based strategy. MATERIALS AND METHODS: Methylation status of the TFPI2 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 TFPI2 gene was detected in 7 out of 38 (18%) primary gastric carcinomas, suggesting that the methylation of TFPI2 is frequently observed in gastric carcinomas. The clinicopathological data were correlated with the methylation results. A significant difference was observed in maximal tumour size (p=0.0084), extent of tumour (p=0.0068), and TNM stage (p=0.0392). CONCLUSION: TFPI2 is frequently methylated in advanced gastric carcinomas.

Methylation of the p16 gene is frequently detected in lymphatic-invasive 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.

Demethylation of the CD133 gene is frequently detected in early gastric carcinoma.

BACKGROUND: Recently, it has been reported that colorectal carcinoma is created and propagated by a small number of undifferentiated tumorigenic CD133(+) cells. Furthermore, it has been reported that CD133 expression is directly regulated by epigenetic modifications. Therefore, it is possible that CD133 expression by gene demethylation is related to colorectal and gastric carcinogenesis. MATERIALS AND METHODS: The methylation status of the CD133 gene was examined in primary carcinomas and the corresponding normal tissues derived from 36 patients with gastric cancer using quantitative methylation-specific polymerase chain reaction (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Demethylation of the CD133 gene was detected in 14 out of the 36 (39%) primary gastric carcinomas, suggesting that the demethylation of CD133 is frequently observed in gastric carcinomas. The clinicopathological data were correlated with the demethylation results. A significant decrease of CD133 methylation was observed in the extent of tumor (p=0.0421). Moreover, a trend was shown toward smaller maximal tumor size in tumors with demethylated CD133 (p=0.0556). CONCLUSION: CD133 appears to be frequently demethylated in early gastric carcinomas.

Methylation of TFPI2 gene is frequently detected in advanced well-differentiated colorectal cancer.

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.

Methylation of the DCC gene is lost in advanced gastric cancer.

BACKGROUND: Deleted in colorectal carcinoma (DCC), one of the Netrin-1 receptors, belongs to the functional dependence receptor family, members of which share the ability to induce apoptosis in the absence of their ligands. Recently, we examined the methylation status of the DCC gene in colorectal carcinomas and found that aberrant methylation of the DCC gene was detected in 28 out of the 50 (56%) primary colon carcinomas. This result prompted us to examine the methylation status of the DCC gene in gastric carcinoma. MATERIALS AND METHODS: The methylation status of the DCC gene was examined in primary carcinomas and the corresponding normal tissues derived from 36 patients with gastric cancer using quantitative methylation-specific polymerase chain reaction (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant methylation of the DCC gene was detected in 16 out of the 36 (44%) primary gastric carcinomas. A significant difference was observed in regard to the TNM stage (p=0.0093). CONCLUSION: DCC methylation was observed in the course of gastric carcinogenesis and disappeared in advanced gastric carcinoma.

Changes in UNC5C gene methylation during human gastric carcinogenesis.

BACKGROUND: UNC5C, one of the netrin-1 receptors, belongs to the functional dependence receptor family, members of which share the ability to induce apoptosis in the absence of their ligands. Recently, aberrant methylation of the UNC5C gene was found in 34 out of 49 (69%) primary colon carcinomas. MATERIALS AND METHODS: The methylation status of the UNC5C gene was examined in primary carcinomas and the corresponding normal tissues derived from 36 patients with gastric cancer using quantitative methylation-specific polymerase chain reaction, and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant methylation of the UNC5C gene was detected in 9 out of the 36 (25%) primary gastric carcinomas. A significant difference was observed in regard to the TNM stage (p=0.0455). CONCLUSION: UNC5C methylation was observed in the course of gastric carcinogenesis and disappeared in highly advanced gastric carcinomas.

Frequent CDH3 demethylation in advanced gastric carcinoma.

BACKGROUND: We recently found that CDH3 was frequently demethylated in advanced colorectal carcinomas. This prompted us to examine the demethylation status of the CDH3 gene in gastric carcinomas. MATERIALS AND METHODS: The demethylation status of the CDH3 gene was examined in primary tumors derived from 36 patients with gastric carcinoma using a quantitative methylation-specific PCR (qMSP) and was evaluated the correlation between the demethylation status and the clinicopathological findings. RESULTS: Demethylation of the CDH3 gene was detected in 25 out of the 36 (69%) primary gastric carcinomas, suggesting that the aberrant demethylation of CDH3 is a frequent event in gastric carcinomas. Demethylation of CDH3 was significantly associated with increasing TNM stage (p=0.0261). Moreover, a trend was shown toward infiltration beyond the serosa being associated with demethylation of CDH3 (p=0.0733). CONCLUSION: CDH3 was frequently demethylated in advanced gastric carcinomas.

Down-regulation of Tip60 gene as a potential marker for the malignancy of colorectal cancer.

BACKGROUND: Recently, it was shown that the loss of human Tip60 leads to an accumulation of double-strand DNA breaks and is linked to a growing number of cancer types. PATIENTS AND METHODS: Tip60 expression levels were in examined in 38 colorectal cancer samples using a quantitative real-time polymerase chain reaction. Subsequently, clinicopathological data were correlated with the Tip60 expression score. RESULTS: A down-regulation of the Tip60 gene was observed 5 out of 38 (13%) specimens of primary colorectal cancer. Tip60 down-regulation showed significant correlation with larger tumor size (p=0.0005), poorly differentiated type (p=0.0394), peritoneal dissemination (p=0.0053), distant metastasis (p=0.0394), and higher stage of TNM classification (p=0.0226). CONCLUSION: These results suggested that Tip60 was more frequently down-regulated in advanced colorectal carcinoma.

Demethylation of the CDH3 gene is frequently detected in advanced colorectal cancer.

BACKGROUND: Recently, it has been proven that the CDH3 promoter was hypomethylated in colonic aberrant foci and colorectal cancer. The hypomethylation was also associated with induction of CDH3 expression in colorectal cancer. These results indicated that epigenetic demethylation of the CDH3 promoter in the human intestine permits its ectopic expression in colorectal cancer. MATERIALS AND METHODS: The demethylation status of the CDH3 gene was examined in primary carcinomas and the corresponding normal tissues derived from 53 patients with colorectal cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the demethylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant demethylation of the CDH3 gene was detected in 41 out of the 53 (77%) primary colon carcinomas. The clinicopathological data were correlated with the demethylation results. A significant difference was observed in the tumor site and Dukes' stage (p=0.0187 and p=0.0192, respectively). Moreover, a trend was shown toward preferentially developing tumor size (p=0.140). CONCLUSION: These results indicated that CDH3 was more frequently demethylated in advanced colorectal carcinomas.

Frequent methylation of Vimentin in well-differentiated gastric carcinoma.

BACKGROUND: Recently, it was shown that the vimentin gene, usually activated in mesenchymal cells, was highly methylated in colorectal carcinoma. MATERIALS AND METHODS: The methylation status of the vimentin gene was examined in primary carcinomas and the corresponding normal tissues derived from 37 patients with gastric carcinoma using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant methylation of the vimentin gene was detected in 14 out of 37 (38%) primary gastric carcinomas. This result suggested that the aberrant methylation of the vimentin gene was frequent in gastric carcinomas. Subsequently, clinicopathological data were correlated with the methylation score. A significant difference was observed in histology (p=0.0429). In addition, a trend was shown toward advancement of gastric carcinomas with vimentin methylation (p=0.0588). CONCLUSION: In gastric carcinomas, well-differentiated adenocarcinoma was significantly methylated compared to poorly differentiated.

Demethylation of the CD133 gene is frequently detected in advanced colorectal cancer.

BACKGROUND: Recently, it has been reported that colorectal carcinoma is created and propagated by a small number of undifferentiated tumorigenic CD133(+) cells. Furthermore, it has been reported that CD133 expression is directly regulated by epigenetic modifications. Therefore, it is possible that CD133 expression by gene demethylation is related to colorectal carcinogenesis. MATERIALS AND METHODS: The methylation status of the CD133 gene was examined in primary carcinomas and the corresponding normal tissues derived from 48 patients with colorectal cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Demethylation of the CD133 gene was detected in 19 out of the 48 (40%) primary colon carcinomas, suggesting that the demethylation of CD133 is frequently observed in colorectal carcinomas. The clinicopathological data were correlated with the demethylation results. A significant difference was observed in the maximal tumor size (p=0.0222). Moreover, a trend was shown toward preferentially developing lymph node metastasis in demethylated tumors (p=0.214). CONCLUSION: CD133 was more frequently demethylated in advanced colorectal carcinomas.

Methylation of HACE1 in gastric carcinoma.

BACKGROUND: We recently examined the methylation status of the HACE1 gene in primary carcinomas derived from 32 patients with colorectal cancer. A significant increase was observed in the maximal tumor size of the tumors with methylated HACE1 (p=0.0304). Moreover, a trend was shown toward preferentially developing lymph node metastasis in the carcinomas with methylated HACE1 (p=0.0612), suggesting that HACE1 might present a malignant potential in colorectal cancer. These results prompted us to examine the methylation status of the HACE1 gene in gastric carcinomas. MATERIALS AND METHODS: The methylation status of the HACE1 gene was examined in primary carcinomas and the corresponding normal tissues derived from 34 patients with gastric carcinoma using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: An aberrant methylation of the HACE1 gene was detected in 9 out of 34 (26%) primary gastric carcinomas. Subsequently, clinicopathological data were tested for correlation with the methylation score. A significant difference was observed in patient gender (p=0.0429). CONCLUSION: HACE1 was frequently methylated in gastric carcinoma derived from male patients.

Methylation of the MGMT gene is frequently detected in advanced gastric carcinoma.

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.