title: Aberrant gene methylation is a biomarker for the detection of cancer cells in peritoneal wash samples from advanced gastric cancer patients.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Surgery, Saga University Faculty of Medicine, Saga, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hiraki
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kitajima
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Koga
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Tanaka
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Hashiguchi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Noshiro
authors.forename: Kohji
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D005240:Feasibility Studies; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D015644:Miocamycin; D061206:Neoplasm Micrometastasis; D009363:Neoplasm Proteins / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics*; D009367:Neoplasm Staging; D010533:Peritoneal Lavage; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000556:secondary; D000075223:Poly-ADP-Ribose Binding Proteins; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics; D044767:Ubiquitin-Protein Ligases; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D065633:Cytochrome P-450 CYP1B1; D004273:DNA, Neoplasm; D008565:Membrane Proteins; D015644:Miocamycin; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; C090121:BNIP3 protein, human; C425300:RASSF2 protein, human; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins; C585496:CYP1B1 protein, human; C412002:CHFR protein, human