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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

Staining pattern of MSH3 protein expression.Heterogeneous MSH3 protein expression (A), demonstrated by expression of both brown (positive) and blue (negative) nuclei upon MSH3 IHC staining. Low MSH3 protein expression was defined as <85% brown staining of cell cores in tumor cells (B) and high MSH3 protein expression was defined as ≥85% brown staining of cell cores in tumor cells (C).
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pone.0124538.g003: Staining pattern of MSH3 protein expression.Heterogeneous MSH3 protein expression (A), demonstrated by expression of both brown (positive) and blue (negative) nuclei upon MSH3 IHC staining. Low MSH3 protein expression was defined as <85% brown staining of cell cores in tumor cells (B) and high MSH3 protein expression was defined as ≥85% brown staining of cell cores in tumor cells (C).

Mentions: The majority of mCRC patients (n = 381, 69.4%) had a high expression of MSH3 in tumor cells (Fig 3). 21.1% of tumors demonstrated nuclear heterogeneity by expression of both positive and negative nuclei upon MSH3 IHC staining (Fig 3A–3C). Both MSH3 expression and EMAST status was known in 139 patients. Heterogeneous or high MSH3 protein expression was not correlated to EMAST status (p = 0.088 and p = 0.856, respectively).


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)

Staining pattern of MSH3 protein expression.Heterogeneous MSH3 protein expression (A), demonstrated by expression of both brown (positive) and blue (negative) nuclei upon MSH3 IHC staining. Low MSH3 protein expression was defined as <85% brown staining of cell cores in tumor cells (B) and high MSH3 protein expression was defined as ≥85% brown staining of cell cores in tumor cells (C).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0124538.g003: Staining pattern of MSH3 protein expression.Heterogeneous MSH3 protein expression (A), demonstrated by expression of both brown (positive) and blue (negative) nuclei upon MSH3 IHC staining. Low MSH3 protein expression was defined as <85% brown staining of cell cores in tumor cells (B) and high MSH3 protein expression was defined as ≥85% brown staining of cell cores in tumor cells (C).
Mentions: The majority of mCRC patients (n = 381, 69.4%) had a high expression of MSH3 in tumor cells (Fig 3). 21.1% of tumors demonstrated nuclear heterogeneity by expression of both positive and negative nuclei upon MSH3 IHC staining (Fig 3A–3C). Both MSH3 expression and EMAST status was known in 139 patients. Heterogeneous or high MSH3 protein expression was not correlated to EMAST status (p = 0.088 and p = 0.856, respectively).

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