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

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

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.

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Authors and Affiliations

  1. Department of Surgery, Saga University Faculty of Medicine, Saga, Japan

    Masatsugu Hiraki MD, PhD, Yoshihiko Kitajima MD, PhD, Yasuo Koga MD, PhD, Tomokazu Tanaka MD, Jun Nakamura MD, PhD, Kazuyoshi Hashiguchi MD, PhD, Hirokazu Noshiro MD, PhD & Kohji Miyazaki MD, PhD

  2. Department of Surgery, National Hospital Organization Higashisaga Hospital, Saga, Japan

    Yoshihiko Kitajima MD, PhD

Authors
  1. Masatsugu Hiraki MD, PhD
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  2. Yoshihiko Kitajima MD, PhD
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  3. Yasuo Koga MD, PhD
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  4. Tomokazu Tanaka MD
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  5. Jun Nakamura MD, PhD
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  6. Kazuyoshi Hashiguchi MD, PhD
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  7. Hirokazu Noshiro MD, PhD
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  8. Kohji Miyazaki MD, PhD
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Corresponding author

Correspondence to Yoshihiko Kitajima MD, PhD.

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Hiraki, M., Kitajima, Y., Koga, Y. et al. Aberrant Gene Methylation Is a Biomarker for the Detection of Cancer Cells in Peritoneal Wash Samples from Advanced Gastric Cancer Patients. Ann Surg Oncol 18, 3013–3019 (2011). https://doi.org/10.1245/s10434-011-1636-0

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  • DOI: https://doi.org/10.1245/s10434-011-1636-0

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