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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

Forest plot for the association of prevalence of EMAST in patients with MSI compared to MSS tumors in stage I-IV CRC.
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pone.0124538.g005: Forest plot for the association of prevalence of EMAST in patients with MSI compared to MSS tumors in stage I-IV CRC.

Mentions: The literature search identified 7 studies in which EMAST was described in stage I-IV CRC patients with MSI and MSS tumors [21–24,27,33,34]. Two studies were excluded: one study described the same population [23] and one study assessed the prevalence of EMAST solely in patients with MSS tumors [27]. Three studies had limited numbers of MSI tumors. Fig 5 summarizes a forest plot of the 5 published studies and the current study on the prevalence of EMAST in stage I-IV CRC patients with MSI and MSS tumors. EMAST is significantly more frequent in tumors with MSI (148/174) (RR 4.80, 95% confidence interval 3.90–5.91). Significant heterogeneity was observed.


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)

Forest plot for the association of prevalence of EMAST in patients with MSI compared to MSS tumors in stage I-IV CRC.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0124538.g005: Forest plot for the association of prevalence of EMAST in patients with MSI compared to MSS tumors in stage I-IV CRC.
Mentions: The literature search identified 7 studies in which EMAST was described in stage I-IV CRC patients with MSI and MSS tumors [21–24,27,33,34]. Two studies were excluded: one study described the same population [23] and one study assessed the prevalence of EMAST solely in patients with MSS tumors [27]. Three studies had limited numbers of MSI tumors. Fig 5 summarizes a forest plot of the 5 published studies and the current study on the prevalence of EMAST in stage I-IV CRC patients with MSI and MSS tumors. EMAST is significantly more frequent in tumors with MSI (148/174) (RR 4.80, 95% confidence interval 3.90–5.91). Significant heterogeneity was observed.

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