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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.


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Flowchart of selected CRC patients to determine the frequency and prognostic value of EMAST.
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pone.0124538.g001: Flowchart of selected CRC patients to determine the frequency and prognostic value of EMAST.

Mentions: Data were derived from mCRC patients included in two large phase III studies: CAIRO (ClinicalTrials.gov NCT00312000) (n = 820) and CAIRO2 (n = 755) (ClinicalTrials.gov NCT00208546), of which the results have been published previously [28,29]. Collection of formalin-fixed paraffin-embedded (FFPE) material of the primary tumor was part of the initial protocol in both studies. To determine the frequency and prognostic value of EMAST in mCRC patients with MSI tumors we selected 50 mCRC patients with MSI tumors treated in both CAIRO studies. Since MSI is relatively rare in mCRC we combined the patients of the CAIRO (n = 19) and the CAIRO2 (n = 31) study. No validation cohort could be selected for MSI patients. To further evaluate the relation between EMAST and MSI, we retrieved 39 tumors from CRC patients (anonymous samples) with known Lynch syndrome (stage I-IV) from our own database (that has been set up conform the guidelines of the local medical ethical committee (Commissie Mensgebonden Onderzoek Radboudumc) with written informed consent of the patients, from which use of tissue is approved for this study). To determine the frequency and prognostic value of EMAST in mCRC patients with MSS tumors we selected 54 patients of the CAIRO study with comparable characteristics (test group). Patients within the test group were all treated with first-line capecitabine monotherapy for at least 3 cycles, localization of the primary tumor in colon or recto- sigmoid which was resected, WHO performance score 0, normal baseline serum lactate dehydrogenase (LDH) concentration, and had not received prior adjuvant chemotherapy. In addition, we randomly selected 40 additional mCRC patients with MSS tumors treated in the same CAIRO study as a validation group. (Fig 1)


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)

Flowchart of selected CRC patients to determine the frequency and prognostic value of EMAST.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0124538.g001: Flowchart of selected CRC patients to determine the frequency and prognostic value of EMAST.
Mentions: Data were derived from mCRC patients included in two large phase III studies: CAIRO (ClinicalTrials.gov NCT00312000) (n = 820) and CAIRO2 (n = 755) (ClinicalTrials.gov NCT00208546), of which the results have been published previously [28,29]. Collection of formalin-fixed paraffin-embedded (FFPE) material of the primary tumor was part of the initial protocol in both studies. To determine the frequency and prognostic value of EMAST in mCRC patients with MSI tumors we selected 50 mCRC patients with MSI tumors treated in both CAIRO studies. Since MSI is relatively rare in mCRC we combined the patients of the CAIRO (n = 19) and the CAIRO2 (n = 31) study. No validation cohort could be selected for MSI patients. To further evaluate the relation between EMAST and MSI, we retrieved 39 tumors from CRC patients (anonymous samples) with known Lynch syndrome (stage I-IV) from our own database (that has been set up conform the guidelines of the local medical ethical committee (Commissie Mensgebonden Onderzoek Radboudumc) with written informed consent of the patients, from which use of tissue is approved for this study). To determine the frequency and prognostic value of EMAST in mCRC patients with MSS tumors we selected 54 patients of the CAIRO study with comparable characteristics (test group). Patients within the test group were all treated with first-line capecitabine monotherapy for at least 3 cycles, localization of the primary tumor in colon or recto- sigmoid which was resected, WHO performance score 0, normal baseline serum lactate dehydrogenase (LDH) concentration, and had not received prior adjuvant chemotherapy. In addition, we randomly selected 40 additional mCRC patients with MSS tumors treated in the same CAIRO study as a validation group. (Fig 1)

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