Promoter hypermethylation of tumor-related genes in peritoneal lavage and the prognosis of patients with colorectal cancer.
OBJECTIVE
The predictive value of free cancer cells in the peritoneal fluid of patients with colorectal cancer (CRC) remain to be elucidated. The aim of this study was to determine the prognostic relevance of the methylation of tumor-related genes detected in the peritoneal lavage fluid (PLF) of patients undergoing a resection for CRC.


METHODS
The promoter methylation pattern of four target genes, CDH1, CDKN2A (p16), MGMT, and APC, was examined in 51 primary CRC and corresponding matched PLF DNA. The relative methylation levels of these genes in primary CRC tissue and paired PLF were assessed by quantitative methylation-specific polymerase chain reaction (QMSP).


RESULTS
An aberrant methylation of at least one gene was found in 45 of 51 (88%) primary tumors. In matched PLF specimens, the frequencies of aberrant promoter methylation detected for each marker were 16% for CDH1, 2% for p16, 4% for MGMT and 24% for APC. Patients with PLF demonstrating the methylation of more than one of these four target genes demonstrated significantly shorter relapse-free survival.


CONCLUSIONS
These findings suggest that disseminated tumor cells in PLF detected by QMSP may correlate with the postoperative clinical course of patients undergoing curative surgery for CRC.
Kamiyama
Hidenori
H
Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
Noda
Hiroshi
H
Takata
Osamu
O
Suzuki
Koichi
K
Kawamura
Yutaka
Y
Konishi
Fumio
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010537:Peritoneum / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic; D007507:Therapeutic Irrigation