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

Venderbosch S, van Lent-van Vliet S, de Haan AF, Ligtenberg MJ, Goossens M, Punt CJ, Koopman M, Nagtegaal ID - PLoS ONE (2015)

Bottom Line: Immunohistochemistry for MSH3 was compared with EMAST status.We found no correlation between EMAST and MSH3 protein expression.A limitation of our study is the small number of patients in our subgroup analysis.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Frequency of instable EMAST markers (A) and frequency of affected EMAST loci (B), subdivided by patients with MSI and MSS tumors.
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pone.0124538.g002: Frequency of instable EMAST markers (A) and frequency of affected EMAST loci (B), subdivided by patients with MSI and MSS tumors.

Mentions: In patients with MSS / EMAST tumors instability was generally shown at 2 EMAST loci (69.2%, 9 out of 13), whereas in patients with MSI / EMAST tumors instability was frequently shown at 4 (33.8%, 24 out of 71), or 5 (50.7%, 36 out of 71) EMAST loci (Fig 2A). The highest frequency of instability in EMAST tumors was demonstrated at the D20S82 locus (91.7%, 77 out of 84), followed by the MYCL1 locus (86.9%, 73 out of 84), the D9S242 locus (84.5%, 71 out of 84), the D8S321 locus (72.6%, 61 out of 84) and the D20S85 locus (65.5%, 55 out of 84) (Fig 2B).


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

Venderbosch S, van Lent-van Vliet S, de Haan AF, Ligtenberg MJ, Goossens M, Punt CJ, Koopman M, Nagtegaal ID - PLoS ONE (2015)

Frequency of instable EMAST markers (A) and frequency of affected EMAST loci (B), subdivided by patients with MSI and MSS tumors.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401564&req=5

pone.0124538.g002: Frequency of instable EMAST markers (A) and frequency of affected EMAST loci (B), subdivided by patients with MSI and MSS tumors.
Mentions: In patients with MSS / EMAST tumors instability was generally shown at 2 EMAST loci (69.2%, 9 out of 13), whereas in patients with MSI / EMAST tumors instability was frequently shown at 4 (33.8%, 24 out of 71), or 5 (50.7%, 36 out of 71) EMAST loci (Fig 2A). The highest frequency of instability in EMAST tumors was demonstrated at the D20S82 locus (91.7%, 77 out of 84), followed by the MYCL1 locus (86.9%, 73 out of 84), the D9S242 locus (84.5%, 71 out of 84), the D8S321 locus (72.6%, 61 out of 84) and the D20S85 locus (65.5%, 55 out of 84) (Fig 2B).

Bottom Line: Immunohistochemistry for MSH3 was compared with EMAST status.We found no correlation between EMAST and MSH3 protein expression.A limitation of our study is the small number of patients in our subgroup analysis.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus