title: EMAST is associated with a poor prognosis in microsatellite instable metastatic colorectal cancer.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, Radboud university medical center, PO Box 9101-6500 HB, Nijmegen, The Netherlands; Department of Medical Oncology, Academic Medical Center, University of Amsterdam, PO Box 22660-1100 DD, Amsterdam, The Netherlands.
authors.forename: Sabine
authors.initials: S
authors.lastname: Venderbosch
authors.affiliation: Department of Pathology, Radboud university medical center, PO Box 9101-6500 HB, Nijmegen, The Netherlands.
authors.forename: Shannon
authors.initials: S
authors.lastname: van Lent-van Vliet
authors.affiliation: Department for Health Evidence, Radboud university medical center, PO Box 9101-6500 HB, Nijmegen, The Netherlands.
authors.forename: Anton F J
authors.initials: AF
authors.lastname: de Haan
authors.affiliation: Department of Pathology, Radboud university medical center, PO Box 9101-6500 HB, Nijmegen, The Netherlands; Department of Human Genetics, Radboud university medical center, PO Box 9101-6500 HB, Nijmegen, The Netherlands.
authors.forename: Marjolijn J
authors.initials: MJ
authors.lastname: Ligtenberg
authors.affiliation: Department of Pathology, Radboud university medical center, PO Box 9101-6500 HB, Nijmegen, The Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: Goossens
authors.affiliation: Department of Medical Oncology, Academic Medical Center, University of Amsterdam, PO Box 22660-1100 DD, Amsterdam, The Netherlands.
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
authors.affiliation: Department of Medical Oncology, University Medical Center Utrecht, PO Box 85500-3508 GA, Utrecht, The Netherlands.
authors.forename: Miriam
authors.initials: M
authors.lastname: Koopman
authors.affiliation: Department of Pathology, Radboud university medical center, PO Box 9101-6500 HB, Nijmegen, The Netherlands.
authors.forename: Iris D
authors.initials: ID
authors.lastname: Nagtegaal
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid