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  • Title: Aberrant gene methylation in the lymph nodes provides a possible marker for diagnosing micrometastasis in gastric cancer.
    Author: Hiraki M, Kitajima Y, Sato S, Mitsuno M, Koga Y, Nakamura J, Hashiguchi K, Noshiro H, Miyazaki K.
    Journal: Ann Surg Oncol; 2010 Apr; 17(4):1177-86. PubMed ID: 19957042.
    Abstract:
    BACKGROUND: This study was designed to determine whether gene methylation is a novel diagnostic marker for micrometastasis to the lymph nodes (LNs) in gastric cancer. METHODS: The gene methylation of CHFR, p16, RUNX3, E-cadherin, MGMT, hMLH1, and ABCG2 genes were analyzed in 49 primary gastric cancer tissues, corresponding to noncancerous tissues and matched LNs by quantitative methylation-specific PCR (q-MSP). RESULTS: CHFR, RUNX3, MGMT, and hMLH1 were more frequently methylated in primary cancer compared with the noncancerous mucosa. Further analyses investigated whether the methylation of the four cancer-specific genes was preserved in LN tissues using the 29 control cases, in which LN metastasis had been histologically confirmed. The methylation of both lesions (M/M pattern) in at least one gene, which was judged to be positive for cancer cells in LNs, was observed in 25 of 29 cases (86%). Quantitative RT-PCR (qRT-PCR) of CEA, CK19, and CK20 mRNA was conducted using the same samples. The mRNA expression of at least one of the three genes was observed in 100% of the specimens. The results of the control analysis were used to attempt to predict micrometastasis by q-MSP and qRT-PCR in the 20 test cases without histological LN metastasis. Six cases (30%) showed the M/M pattern in at least one of the four genes. Three of 20 cases (15%) exhibited both the M/M pattern and positive mRNA. CONCLUSIONS: The methylation analysis revealed the clinical feasibility of detecting occult neoplastic cells in the regional LNs.
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