EMAST is associated with a poor prognosis in microsatellite instable metastatic colorectal cancer

Sabine Venderbosch, Shannon Van Lent-van Vliet, Anton F.J. De Haan, Marjolijn J. Ligtenberg, Monique Goossens, Cornelis J.A. Punt, Miriam Koopman, Iris D. Nagtegaal

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)

Abstract

Purpose: To determine the frequency and prognostic value of elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) in metastatic colorectal cancer (mCRC) patients in relation to microsatellite instability (MSI) status and MSH3 protein expression. Material and Methods: The frequency of EMAST was evaluated in mCRC patients with MSI tumors and microsatellite stable (MSS) tumors. A literature overview was performed to compare the frequency of EMAST in our study with existing data. Immunohistochemistry for MSH3 was compared with EMAST status. Outcome was studied in terms of overall survival (OS) of mCRC patients with MSI and MSS tumors. Results: EMAST was evaluated in 89 patients with MSI tumors (including 39 patients with Lynch syndrome) and 94 patients with MSS tumors. EMAST was observed in 45.9% (84 out of 183) of patients, with an increased frequency in MSI tumors (79.8% versus 13.8%, p < 0.001). We found no correlation between EMAST and MSH3 protein expression. There was no effect of EMAST on prognosis in patients with MSS tumors, but patients with MSI / non-EMAST tumors had a significantly better prognosis than patients with MSI / EMAST tumors (OS: HR 3.22, 95% CI 1.25-8.30). Conclusion: Frequency of EMAST was increased in mCRC patients with MSI tumors, compared to MSS tumors. Our data suggest that the presence of EMAST correlates with worse OS in these patients. There was no effect of EMAST on the prognosis of patients with MSS tumors. A limitation of our study is the small number of patients in our subgroup analysis.

Original languageEnglish
Article numbere0124538
JournalPLoS ONE [E]
Volume10
Issue number4
DOIs
Publication statusPublished - 2015

Keywords

  • Colorectal Neoplasms
  • DNA Methylation
  • Female
  • Humans
  • Male
  • Microsatellite Repeats
  • Neoplasm Metastasis
  • Prognosis
  • Promoter Regions, Genetic
  • Repetitive Sequences, Nucleic Acid
  • Journal Article
  • Research Support, Non-U.S. Gov't

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