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

doi:10.1371/journal.pone.0124538

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

PLoS One. 2015 Apr 17;10(4):e0124538. doi: 10.1371/journal.pone.0124538. eCollection 2015.

Authors

Sabine Venderbosch¹, Shannon van Lent-van Vliet², Anton F J de Haan³, Marjolijn J Ligtenberg⁴, Monique Goossens², Cornelis J A Punt⁵, Miriam Koopman⁶, Iris D Nagtegaal²

Affiliations

¹ 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.
² Department of Pathology, Radboud university medical center, PO Box 9101-6500 HB, Nijmegen, The Netherlands.
³ Department for Health Evidence, Radboud university medical center, PO Box 9101-6500 HB, Nijmegen, The Netherlands.
⁴ 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.
⁵ Department of Medical Oncology, Academic Medical Center, University of Amsterdam, PO Box 22660-1100 DD, Amsterdam, The Netherlands.
⁶ Department of Medical Oncology, University Medical Center Utrecht, PO Box 85500-3508 GA, Utrecht, The Netherlands.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Colorectal Neoplasms / genetics*
Colorectal Neoplasms / pathology
DNA Methylation
Female
Humans
Male
Microsatellite Repeats / genetics*
Neoplasm Metastasis / genetics*
Prognosis
Promoter Regions, Genetic
Repetitive Sequences, Nucleic Acid*

Grants and funding

This study was supported by a grant from the Dutch Colorectal Cancer Group (DCCG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.