Clinical application of methylation specific-polymerase chain reaction in serum of patients with gastric cancer.
OBJECTIVE
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).


METHODS
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.
Ikoma
Hisashi
H
Department of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Ichikawa
Daisuke
D
Daito
Ikoma
I
Nobuyuki
Tani
T
Koike
Hiroshi
H
Okamoto
Kazuma
K
Ochiai
Toshiya
T
Ueda
Yuji
Y
Yamagishi
Hisakazu
H
Otsuji
Eigo
E
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D016133:Polymerase Chain Reaction / Q000379:methods*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D013274:Stomach Neoplasms / Q000175:diagnosis*
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta