PURPOSE: This study was designed to detect aberrant p16 promoter methylation in the serum of patients with colorectal cancer (CRC) and to explore the possibility of using this assay in early detection or as a prognostic marker of CRC patients. EXPERIMENTAL DESIGN: Methylation-specific PCR was used to detect p16 methylation in DNA extracted from 52 CRCs and matching serum samples and control serum samples from 34 patients with adenomatous polyps and 10 healthy individuals. The association of p16 hypermethylation in serum DNA of CRC patients with clinicopathological characteristics was then analyzed. RESULTS: P16 hypermethylation was found in 20 of 52 (38%) CRCs. Among the 20 cases with aberrant methylation in the tumor tissues, similar changes were also detected in the serum of 14 (70%) cases. No methylated p16 sequences were detected in the peripheral serum of the other 32 CRC cases without these changes in the tumor, in 34 patients with adenomatous polyps, or in 10 healthy control subjects. Clinicopathological analysis revealed that p16 methylation in serum was significantly associated with later Dukes' stage (P = 0.03). CONCLUSIONS: This assay offers a potential means for the serum-based detection and/or monitoring of CRC patients.
PURPOSE: This study was designed to detect aberrant p16 promoter methylation in the serum of patients with colorectal cancer (CRC) and to explore the possibility of using this assay in early detection or as a prognostic marker of CRCpatients. EXPERIMENTAL DESIGN: Methylation-specific PCR was used to detect p16 methylation in DNA extracted from 52 CRCs and matching serum samples and control serum samples from 34 patients with adenomatous polyps and 10 healthy individuals. The association of p16 hypermethylation in serum DNA of CRCpatients with clinicopathological characteristics was then analyzed. RESULTS:P16 hypermethylation was found in 20 of 52 (38%) CRCs. Among the 20 cases with aberrant methylation in the tumor tissues, similar changes were also detected in the serum of 14 (70%) cases. No methylated p16 sequences were detected in the peripheral serum of the other 32 CRC cases without these changes in the tumor, in 34 patients with adenomatous polyps, or in 10 healthy control subjects. Clinicopathological analysis revealed that p16 methylation in serum was significantly associated with later Dukes' stage (P = 0.03). CONCLUSIONS: This assay offers a potential means for the serum-based detection and/or monitoring of CRCpatients.
Authors: Susan E Cottrell; Jürgen Distler; Nancy S Goodman; Suzanne H Mooney; Antje Kluth; Alexander Olek; Ina Schwope; Reimo Tetzner; Heike Ziebarth; Kurt Berlin Journal: Nucleic Acids Res Date: 2004-01-13 Impact factor: 16.971