Background/aims: We previously reported that aberrant methylation of p16 and/or E-cadherin genes in serum DNA could serve together as a tumor marker in gastric cancer. We presently investigated whether sensitivity could be increased by consideration of a third gene, which encodes retinoic acid receptor-1 (RARbeta).
Methodology: We performed a methylation-specific polymerase chain reaction (MSP) in serum DNA to detect aberrant methylation of RARbeta from 109 preoperative gastric cancer patients, in which the first two genes had been characterized. We also examined all three genes in sera from 10 outpatients during postgastrectomy follow-up.
Results: Aberrant methylation of RARbeta was demonstrated in 26 preoperative patients (24%). Considering this with previous results, 52 patients (48%) of the 109 preoperative showed hypermethylation of at least one gene (p16, E-cadherin, and/or RARbeta). No aberrant methylation was detected in control sera. In the follow-up group, aberrant methylation was demonstrated in 2 of the 3 patients who had definite radiologic evidence of recurrences. One of the patients showing promoter hypermethylation without definite findings of recurrence at the time of analysis developed peritoneal recurrence 6 months later.
Conclusions: Including the MSP assay in conventional follow-up could facilitate early detection of recurrent disease in gastric cancer patients.