Promoter Hypermethylation of Tumor-Related Genes in Peritoneal Lavage and the Prognosis of Patients With Colorectal Cancer

Background and Objectives: 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 (p 16), 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 p 16, 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 cot-relate with the postoperative clinical course of patients Undergoing curative surgery for CRC. J. Surg. Oncol. 2009; 100: 69-74. (C) 2009 Wiley-Liss, Inc.