Quantitative SEPT9 Methylation in Colorectal and Endometrial Cancers Suspected of Lynch Syndrome.

Abstract

Introduction: Lynch syndrome (LS) is associated with increased risks of colorectal cancer (CRC), endometrial cancer (EC), and other malignancies. This exploratory study evaluated quantitative SEPT9 promoter methylation in archived tumor tissue and whole blood from patients with suspected LS.

Methods: In this retrospective observational study with cross-sectional molecular analysis, DNA from 22 paired formalin-fixed paraffin-embedded (FFPE) tumors and 22 matched EDTA whole-blood specimens (17 CRC and 5 EC) was analyzed. Methylation at five SEPT9 CpG sites was quantified by bisulfite pyrosequencing following nested PCR amplification. Tissue-blood methylation-status concordance was assessed descriptively using a ≥5% threshold.

Results: Whole-blood SEPT9 methylation was higher in CRC than in EC (P<0.01), with relatively prominent signals at CpG2 and CpG4. Tissue-blood concordance was 59.1% overall (13/22), 58.8% in CRC (10/17), and 60.0% in EC (3/5). Within CRC, concordance was 16.7% in early-stage disease (1/6) and 66.7% in advanced-stage disease (8/11). These findings were exploratory and descriptive.

Discussion: The observed stage-related pattern and tissue-blood concordance support further investigation of quantitative SEPT9 methylation as a complementary marker. The small cohort and exploratory nature of the thresholds preclude conclusions regarding diagnostic or prognostic performance.

Conclusion: Quantitative SEPT9 methylation was detectable in archived FFPE tumors and whole blood from LS-suspected patients. Larger prospective studies are required to validate the observed differences and determine their clinical relevance.