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

Masatsugu Hiraki MD, Yoshihiko Kitajima MD, PhD, Seiji Sato MD, PhD, Mayumi Mitsuno MD, PhD, Yasuo Koga MD, PhD, Jun Nakamura MD, Kazuyoshi Hashiguchi MD, Hirokazu Noshiro MD, PhD, Kohji Miyazaki MD, PhD
Translational Research and Biomarkers
Volume 17, Issue 4 / April , 2009

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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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