Aberrant Gene Methylation in the Lymph Nodes Provides a Possible Marker for Diagnosing Micrometastasis in Gastric Cancer

作者：Hiraki Masatsugu^*; Kitajima Yoshihiko; Sato Seiji; Mitsuno Mayumi; Koga Yasuo; Nakamura Jun; Hashiguchi Kazuyoshi; Noshiro Hirokazu; Miyazaki Kohji

来源：Annals of Surgical Oncology, 2010, 17(4): 1177-1186.

DOI：10.1245/s10434-009-0815-8

This study was designed to determine whether gene methylation is a novel diagnostic marker for micrometastasis to the lymph nodes (LNs) in gastric cancer.
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).
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.
The methylation analysis revealed the clinical feasibility of detecting occult neoplastic cells in the regional LNs.

• 出版日期2010-4