Aberrant Gene Methylation Is a Biomarker for the Detection of Cancer Cells in Peritoneal Wash Samples from Advanced Gastric Cancer Patients

• Published in: Annals of surgical oncology Vol. 18; no. 10; pp. 3013 - 3019
• Main Authors: Hiraki, Masatsugu, Kitajima, Yoshihiko, Koga, Yasuo, Tanaka, Tomokazu, Nakamura, Jun, Hashiguchi, Kazuyoshi, Noshiro, Hirokazu, Miyazaki, Kohji
• Format: Journal Article
• Language: English
• Published: New York Springer-Verlag 01.10.2011; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Aryl Hydrocarbon Hydroxylases - genetics; Biomarkers, Tumor - genetics; Cell Cycle Proteins - genetics; Cytochrome P-450 CYP1B1; DNA Methylation; DNA, Neoplasm - genetics; Feasibility Studies; Female; Gastric Mucosa - metabolism; Gastric Mucosa - pathology; Humans; Male; Medicine; Medicine & Public Health; Membrane Proteins - genetics; Middle Aged; Miocamycin; Neoplasm Micrometastasis; Neoplasm Proteins - genetics; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - genetics; Neoplasm Staging; Oncology; Peritoneal Lavage; Peritoneal Neoplasms - genetics; Peritoneal Neoplasms - secondary; Poly-ADP-Ribose Binding Proteins; Polymerase Chain Reaction; Prognosis; Proto-Oncogene Proteins - genetics; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Surgery; Surgical Oncology; Survival Rate; Translational Research and Biomarkers; Tumor Cells, Cultured; Tumor Suppressor Proteins - genetics; Ubiquitin-Protein Ligases; Gastric Cancer; Peritoneal Metastasis; Gastric Cancer Patient; Methylation Level; Methylation Status
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-011-1636-0

Purpose To assess whether gene methylation in peritoneal fluid (PF) is clinically feasible for determining micrometastasis to the peritoneum in gastric cancer. Methods The gene methylation of BNIP3, CHFR, CYP1B1, MINT25, SFRP2, and RASSF2 were analyzed in 107 specimens of PF by quantitative methylation-specific polymerase chain reaction. All patients were placed into one of 3 groups: group A ( n  = 42), patients with depth of cancer invasion at muscularis propria (MP) or less than MP; group B ( n  = 45), depth of cancer invasion beyond the MP; and group C ( n  = 20), histologically diagnosed peritoneal metastasis or cancer cells cytologically defined in the peritoneal cavity. Patients in both groups A and B were diagnosed as having no cancer cells by peritoneal cytology and histology. Results The methylation status of the 6 genes was found to be significantly different among the 3 groups (group A, 0–5%; group B, 0–15%; group C, 15–45%; P  < 0.01). Furthermore, the rate of positive methylation in any of the 6 genes was significantly different in each group (group A, 7%; group B, 20%; group C, 75%; P  < 0.001). Three of 9 patients in group B with positive methylation in any of 6 genes experienced peritoneal recurrence. On the other hand, only 1 of 36 patients without gene methylation experienced peritoneal recurrence ( P  < 0.05). Conclusions DNA methylation in PFs is a possible marker detecting occult neoplastic cells on the peritoneum. Methylation analysis along with a cytological examination might therefore improve the positive detection of cancer cells in PF of gastric cancer.