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Detection of Minimal Gastric Cancer Cells in Peritoneal Washings by Focused Microarray Analysis with Multiple Markers: Clinical Implications

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Peritoneal cytology is an important prognostic factor of gastric cancer. However, peritoneal cytology requires great skill, which may explain its low prevalence. A reverse transcriptase–polymerase chain reaction–based assay with multiple marker genes or immunocytochemistry was assessed as an alternative method of gathering the same kind of data as cytology.

Methods

Peritoneal washings from 179 patients with gastric cancer were analyzed by multiplex reverse transcriptase–polymerase chain reaction with 10 marker genes and subsequent hybridization to a customized oligo-nucleotide array. Results with this assay were either validated as a prognostic factor or confirmed by demonstrating the presence of cancer cells by immunocytochemical cytology.

Results

Only 1 (2.2%) of 44 disease-free cases was shown to be positive by the microarray assay, whereas 13 (93%) of 14 conventional cytology–positive cases were found to be positive. This assay further detected approximately one-third of cytology-negative patients either with peritoneal recurrence (7 of 20, 35%) or with non-peritoneal recurrence (6 of 22, 27%). A high concordance between the microarray assay and immunocytochemical cytology with five antibodies against CK20, FABP1, MUC2, TFF1, and MASPIN was confirmed. The clinical outcome of the microarray assay–positive cases was poor, as was that of the cytology-positive cases.

Conclusions

Our assay, though time-consuming and requiring special equipment, demonstrated a specificity and sensitivity equal to or better than cytology in our institutes. The minimal free peritoneal cancer cells detected by the microarray assay may provide the same clinical information as larger amounts of cancer cells for patients with gastric cancer. An anti-MASPIN antibody may be helpful in peritoneal cytology of gastric cancer.

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Acknowledgments

Supported in part by a grant from the program for the Promotion of Fundamental Studies in Health Sciences of the National Institute of Biochemical Innovation (NiBio); and by a Grant-in-Aid for the Third Comprehensive 10-Year Strategy for Cancer Control and for Cancer Research (15-5 and 16-15) from the Ministry of Health, Labour and Welfare of Japan. K.M. was a recipient of Research Resident Fellowships from the Foundation for Promotion of Cancer Research. We thank Mr. Kiyoaki Nomoto for his assistance in immunocytochemistry.

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Authors and Affiliations

  1. Department of Gastrointestinal Surgery, University of Tokyo Graduate School of Medicine, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan

    Kazuhiko Mori MD, Tetsuya Ueda MD & Michio Kaminishi MD

  2. Department of Pathology, University of Tokyo Graduate School of Medicine, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan

    Hiroshi Uozaki MD

  3. Nanotechnology and Advanced System Research Laboratories, Canon Inc., Shimomaruko 3-30-2, Ohta-ku, Tokyo, 146-8501, Japan

    Tomohiro Suzuki PhD & Nobuko Yamamoto PhD

  4. Laboratory of Pathology, Aichi Cancer Center Research Institute, Aichi Cancer Center Hospital, Kanokoden 1-1, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan

    Hayao Nakanishi MD

  5. Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan

    Yasuhiro Kodera MD

  6. Genetics Division, National Cancer Center Research Institute, National Cancer Center, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan

    Kazuhiko Mori MD, Hiromi Sakamoto PhD & Hiroki Sasaki PhD

  7. Clinical Laboratory, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan

    Yoshihiro Matsuno MD

  8. Surgical Oncology Department, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan

    Mitsuru Sasako MD

Authors
  1. Kazuhiko Mori MD
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  2. Tomohiro Suzuki PhD
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  3. Hiroshi Uozaki MD
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  4. Hayao Nakanishi MD
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  5. Tetsuya Ueda MD
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  6. Yoshihiro Matsuno MD
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  7. Yasuhiro Kodera MD
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  8. Hiromi Sakamoto PhD
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  9. Nobuko Yamamoto PhD
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  10. Mitsuru Sasako MD
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  11. Michio Kaminishi MD
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  12. Hiroki Sasaki PhD
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Corresponding author

Correspondence to Hiroki Sasaki PhD.

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Mori, K., Suzuki, T., Uozaki, H. et al. Detection of Minimal Gastric Cancer Cells in Peritoneal Washings by Focused Microarray Analysis with Multiple Markers: Clinical Implications. Ann Surg Oncol 14, 1694–1702 (2007). https://doi.org/10.1245/s10434-006-9321-4

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  • DOI: https://doi.org/10.1245/s10434-006-9321-4

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