Original Article
Copyright ©2010 Baishideng. All rights reserved
World J Gastroenterol. Jan 21, 2010; 16(3): 330-338
Published online Jan 21, 2010. doi: 10.3748/wjg.v16.i3.330
Aberrant gene methylation in the peritoneal fluid is a risk factor predicting peritoneal recurrence in gastric cancer
Masatsugu Hiraki, Yoshihiko Kitajima, Seiji Sato, Jun Nakamura, Kazuyoshi Hashiguchi, Hirokazu Noshiro, Kohji Miyazaki
Masatsugu Hiraki, Yoshihiko Kitajima, Seiji Sato, Jun Nakamura, Kazuyoshi Hashiguchi, Hirokazu Noshiro, Kohji Miyazaki, Department of Surgery, Saga University Faculty of Medicine, 5-1-1 Nabeshima, Saga 849-8501, Japan
Author contributions: Hiraki M, Kitajima Y and Miyazaki K designed this study; Hiraki M performed all of the experiments and analyzed the data; Hiraki M interpreted the analyzed data and wrote the manuscript under the supervision of Kitajima Y; Nakamura J, Hashiguchi K, Sato S and Noshiro H contributed to the sample collection and advice concerning the study; Miyazaki K approved the final version of the manuscript.
Supported by Fund from the Department of Surgery, Saga University Faculty of Medicine
Correspondence to: Dr. Kohji Miyazaki, MD, PhD, Professor, Department of Surgery, Saga University Faculty of Medicine, 5-1-1 Nabeshima, Saga 849-8501, Japan. miyazak2@cc.saga-u.ac.jp
Telephone: +81-952-342349 Fax: +81-952-342019
Received: October 13, 2009
Revised: November 23, 2009
Accepted: November 30, 2009
Published online: January 21, 2010
Abstract

AIM: To investigate whether gene methylation in the peritoneal fluid (PF) predicts peritoneal recurrence in gastric cancer patients.

METHODS: The gene methylation of CHFR (checkpoint with forkhead and ring finger domains), p16, RUNX3 (runt-related transcription factor 3), E-cadherin, hMLH1 (mutL homolog 1), ABCG2 (ATP-binding cassette, sub-family G, member 2) and BNIP3 (BCL2/adenovirus E1B 19 kDa interacting protein 3) were analyzed in 80 specimens of PF by quantitative methylation-specific polymerase chain reaction (PCR). Eighty patients were divided into 3 groups; Group A (n = 35): the depth of cancer invasion was less than the muscularis propria; Group B (n = 31): the depth of cancer invasion was beyond the muscularis propria. Both group A and B were diagnosed as no cancer cells in peritoneal cytology and histology; Group C (n = 14): disseminated nodule was histologically diagnosed or cancer cells were cytologically defined in the peritoneal cavity.

RESULTS: The positive rates of methylation in CHFR, E-cadherin and BNIP3 were significantly different among the 3 groups and increased in order of group A, B and C (0%, 0% and 21% in CHFR, P < 0.05; 20%, 45% and 50% in E-cadherin, P < 0.05; 26%, 35% and 71% in BNIP3, P < 0.05). In addition, the multigene methylation rate among CHFR, E-cadherin and BNIP3 was correlated with group A, B and C (9%, 19% and 57%, P < 0.001). Moreover, the prognosis was analyzed in group B, excluding 3 patients who underwent a non-curative resection. Two of the 5 patients with multigene methylation showed peritoneal recurrence after surgery, while those without or with a single gene methylation did not experience recurrence (P < 0.05).

CONCLUSION: This study suggested that gene methylation in the PF could detect occult neoplastic cells in the peritoneum and might be a risk factor for peritoneal metastasis.

Keywords: Ascites, Dissemination, Gastric cancer, Methylation, Peritoneal fluid, Quantitative methylation-specific polymerase chain reaction