Stool methylated DNA markers decrease following colorectal cancer resection--implications for surveillance.

BACKGROUND:Molecular changes associated with colorectal cancer (CRC) are detected by stool deoxyribonucleic acid testing but could persist following tumor resection. AIMS:We sought to determine whether methylated gene markers in stool normalize after CRC resection. METHODS:We studied stools from 22 CRC cases before and after subtotal resection and from 80 colonoscopy-normal controls. In blinded fashion, target genes (methylated NDRG4 and BMP3) were captured from stool supernatant, bisulfite-treated, and assayed by quantitative allele-specific real-time target and signal amplification. Results were dichotomized at 95% specificity cutoffs. RESULTS:Among CRC cases, median methylated NDRG4 and BMP3 levels decreased dramatically (4- to 15-fold) following resection, p = 0.003 and p < 0.0001, respectively. Among the 14 cases with elevated preoperative levels, 13 (93%) fell into the normal range after surgery, p = 0.0002. A case whose stool methylated NDRG4 level increased sharply after surgery was found to have recurrent CRC. CONCLUSIONS:Methylated gene marker levels clear from stool following CRC resection unless disease is present. Postoperative stool marker levels are informative and may be of value in surveillance.

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