Epithelial-speci c SHP1-P2 Methylation - a Novel Universal Tumor Marker for Detection of Colorectal Cancer Lymph Node Metastasis


Center of Excellence in Molecular Genetics of Cancer and Human Disease, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Bangkok, Thailand


Background Methylation of promoter 2 of the SHP1 gene is epithelial cell speci c, with reported potential as a lymph node metastatic marker. Objective To demonstrate SHP1-P2 methylation-speci c quantitative PCR effectiveness in detecting colorectal cancer (CRC) DNA in lymph nodes. Materials and Methods SHP1-P2 methylation levels were measured in lymph nodes of CRC patients and compared with pathological ndings and patient prognosis. Results Lymph nodes of CRC metastatic patients without microscopically detectable cancer cells had higher SHP1-P2 methylation levels than lymph nodes of controls (<0.001). In addition, a higher SHP1-P2 methylation level was associated with a shorter duration until adverse disease events, metastasis, recurrence and death (r2 0.236 and p value 0.048). Studying two cohorts of 74 CRC patients without microscopic lymph node metastases showed that only the cohort containing samples with high SHP1-P2 methylation levels had a signi cant hazard ratio of 3.8 (95%CI 1.02 to 14.2). Conclusions SHP1-P2 methylation PCR can detectCRC cancer DNA in lymph nodes even if cancer cells are not visible under a microscope, con rming it's potential universal lymph node metastatic marker.