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Cancer
Microsatellite instability in patients with multiple primary cancers of the gastrointestinal tract
  1. K Yamashitaa,
  2. Y Arimuraa,
  3. S Kurokawaa,
  4. F Itoha,
  5. T Endoa,
  6. K Hiratab,
  7. A Imamurac,
  8. M Kondod,
  9. T Satoe,
  10. K Imaia
  1. aFirst Department of Internal Medicine, Sapporo Medical University, Sapporo, Japan, bFirst Department of Surgery, Sapporo Medical University, Sapporo, Japan, cDepartment of Gastroenterology, Sapporo Kosei General Hospital, Sapporo, Japan, dDepartment of Surgery, Sapporo Kosei General Hospital, Sapporo, Japan, eDepartment of Clinical Pathology, Sapporo Kosei General Hospital, Sapporo, Japan
  1. K Yamashita, First Department of Internal Medicine, Sapporo Medical University, S1W16, Chuo-ku, Sapporo, Japan. Email:kentaroh{at}wa2.so-net.ne.jp

Abstract

BACKGROUND Little is known about the genetic alterations in multiple primary cancers of the gastrointestinal tract. Microsatellite instability (MSI) is frequently observed in hereditary non-polyposis colorectal cancer (HNPCC), and multiple primary cancers is a feature of this syndrome.

AIMS To identify MSI incidence, target gene mutation, and mismatch repair (MMR) protein status in patients with multiple primary cancers of the gastrointestinal tract.

SUBJECTS Fifty seven cancers from 22 Japanese patients with multiple primary cancers of the stomach, duodenum, colon, and rectum.

METHODS MSI was examined at 5–7 microsatellite loci. Mutation analysis for TGFβRII, IGFIIR, and BAX was performed in cancers with MSI. MMR protein status was examined by immunohistochemical analysis using a monoclonal antibody against hMSH2 and hMLH1.

RESULTS MSI was observed in 16 of 22 patients (73%) and in 29 of 57 lesions (51%). High frequency MSI (MSI-H) was found often in patients with multiple cancers in the same organ (p=0.042), especially in multiple gastric cancer patients (p=0.038). In contrast, patients with multiple cancers in different organs had a tendency to show low frequency MSI (MSI-L) or microsatellite stable (MSS) phenotype. Both target gene mutation and decreased expression of MMR protein were found only in seven lesions of three patients with MSI at more than four microsatellite loci.

CONCLUSIONS These results suggest that genetic instability may play an important role in the development of multiple gastrointestinal cancers but there may be different genetic alterations between multiple gastrointestinal cancers of the same and different organs.

  • microsatellite instability
  • multiple primary cancer
  • hereditary non-polyposis colorectal cancer

https://doi.org/10.1136/gut.46.6.790

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    Footnotes

    • Abbreviations used in this paper:
      MSI
      microsatellite instability
      MSS
      microsatellite stable
      HNPCC
      hereditary non-polyposis colorectal cancer
      MMR
      mismatch repair
      PCR polymerase chain reaction
      SSCP, single strand conformation polymorphism