Enhanced Molecular Staging of Pancreatic Cancer Using Methylated DNA Markers in Peritoneal Lavage Fluid.

BACKGROUND AND

OBJECTIVES

Occult intra-abdominal metastases are identified in approximately 20% of patients with radiographically localized pancreatic ductal adenocarcinoma (PDAC) through staging laparoscopy, as peritoneal cytology is limited in sensitivity. Methylated DNA markers (MDMs) have demonstrated high diagnostic accuracy for PDAC in tumor tissue, blood, and pancreatic secretions. This study assesses the feasibility and diagnostic performance of MDMs in peritoneal lavage fluid collected during staging laparoscopy, comparing their performance to mutant KRAS (mKRAS) detection.

METHODS

DNA from peritoneal lavage fluid of PDAC patients was analyzed for mKRAS mutations (codons 12, 13, and 61) using droplet-digital PCR and for 13 MDMs and a reference gene (B3GALT6) using quantitative methylation-specific PCR. An MDM score was generated from the average signal of the 13 MDMs and evaluated for its ability to detect intra-abdominal metastases via receiver operator characteristic (ROC) analysis.

RESULTS

Among 48 patients, 15 (31%) had intra-abdominal metastases. The MDM score showed 87% sensitivity and 90% specificity (AUC = 0.98), outperforming mKRAS, which showed 40% sensitivity and 85% specificity (AUC = 0.62; p < 0.0001).

CONCLUSIONS

MDMs in peritoneal lavage fluid may enable highly accurate molecular staging of PDAC and warrant validation in larger studies.