Testing region selection and prognostic analysis of promoter methylation in colorectal cancer in China.

Background: promoter methylation analysis is recommended in screening for Lynch syndrome (LS) in patients with MLH1-deficient colorectal cancer (CRC). The study aims to identify specific methylation regions in the promoter and to evaluate the clinicopathologic characteristics of and prognosis for patients with methylation.

Methods: A total of 580 CRC cases were included. The DNA mismatch repair (MMR) protein expression was assessed by using immunohistochemistry (IHC). The methylation status of the Regions A, B, C, D, and E in the promoter was tested by using bisulfite sequencing PCR. The specificities of the five regions were calculated. Associations between methylation and clinicopathologic characteristics were evaluated. Kaplan-Meier analyses for overall survival (OS) were carried out.

Results: In 580 CRC cases, the specificities of the methylation test in Regions D and E were both 97.8%. In the MLH1-deficient CRCs, the frequencies of methylation and mutation were 52.6% and 14.6%, respectively; mutation occurred in 27.7% of patients with -methylated CRC. In the MMR-deficient patients, compared with unmethylation, methylation was more common in patients who were aged ≥50 years, female, had no family history of LS-related tumors, and had tumors located at the right colon. In the MMR-deficient patients, the -methylated cases had lower OS rates than the unmethylated cases with a family history of LS-related tumors (=0.047).

Conclusions: Regions D and E in the promoter are recommended for determining the methylation status in screening for LS in MLH1-deficient CRC. In MMR-deficient patients, the -methylated cases had a worse OS than the unmethylated cases with a family history of LS-related cancer.