Microsatellite instability in esophageal adenocarcinoma

Susan C. Evans, Amy Gillis, Laurette Geldenhuys, Nadine M. Vaninetti, Dickran A. Malatjalian, Geoffrey A. Porter, Duane L. Guernsey, Alan G. Casson

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

27 Citas (Scopus)

Resumen

The frequency of microsatellite instability (MSI), a result of defective mismatch repair during DNA replication, has been reported inconsistently in primary esophageal adenocarcinoma (EADC). Using a panel of 15 markers, the primary aim of this study was to analyze the frequency of MSI in a well-characterized series of 27 primary EADCs, defined according to strict clinicopathologic criteria. Polymerase chain reaction was used to amplify the following microsatellite repeat loci: D2S123, D10S197, D2S119, D11S904, D2S147, D3S1764, D7S1830, D7S1805, D2S434, D9S299, BAT25, BAT26, D5S346, D17S250, and TGF-β-RII. Tumors were classified as microsatellite-stable (MSS) when no alterations were seen in tumor DNA compared to matched normal tissues, low-level MSI (MSI-L) when 1-5 of 15 markers were altered, and high-level MSI (MSI-H) when more than five markers were altered. Using these stringent criteria, 9/27 (33%) tumors were MSS, 18/27 (67%) tumors were MSI-L, and no tumor was MSI-H. Immunohistochemistry demonstrated cell nuclear expression of DNA mismatch repair proteins (both hMLH1 and hMSH2) in 78% (21/27) of tumors. No associations were seen between MSI and immunohistochemical expression of hMLH1, hMSH2, alterations in p53 or MBD4, tumor grade, pathologic stage, or patient survival. In conclusion, the finding of low levels of MSI in most tumors suggests an inherent baseline genomic instability, and potentially increased susceptibility to mutations during the progression of esophageal adenocarcinoma.

Idioma originalEnglish
Páginas (desde-hasta)241-251
Número de páginas11
PublicaciónCancer Letters
Volumen212
N.º2
DOI
EstadoPublished - ago. 30 2004

Nota bibliográfica

Funding Information:
This study was funded in part by Nova Scotia Health Research Foundation, the Dalhousie University Department of Surgery, the Dalhousie Cancer Research Program, and the National Cancer Institute of Canada with funds from the Canadian Cancer Society. AGC is supported by a Senior Clinical Research Scholarship from the Dalhousie University Faculty of Medicine.

ASJC Scopus Subject Areas

  • Oncology
  • Cancer Research

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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