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Deficient mismatch repair system in patients with sporadic advanced colorectal cancer

A deficient mismatch repair system (dMMR) is present in 10–20% of patients with sporadic colorectal cancer (CRC) and is associated with a favourable prognosis in early stage disease. Data on patients with advanced disease are scarce. Our aim was to investigate the incidence and outcome of sporadic d...

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Autores principales: Koopman, M, Kortman, G A M, Mekenkamp, L, Ligtenberg, M J L, Hoogerbrugge, N, Antonini, N F, Punt, C J A, van Krieken, J H J M
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2634718/
https://www.ncbi.nlm.nih.gov/pubmed/19165197
http://dx.doi.org/10.1038/sj.bjc.6604867
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author Koopman, M
Kortman, G A M
Mekenkamp, L
Ligtenberg, M J L
Hoogerbrugge, N
Antonini, N F
Punt, C J A
van Krieken, J H J M
author_facet Koopman, M
Kortman, G A M
Mekenkamp, L
Ligtenberg, M J L
Hoogerbrugge, N
Antonini, N F
Punt, C J A
van Krieken, J H J M
author_sort Koopman, M
collection PubMed
description A deficient mismatch repair system (dMMR) is present in 10–20% of patients with sporadic colorectal cancer (CRC) and is associated with a favourable prognosis in early stage disease. Data on patients with advanced disease are scarce. Our aim was to investigate the incidence and outcome of sporadic dMMR in advanced CRC. Data were collected from a phase III study in 820 advanced CRC patients. Expression of mismatch repair proteins was examined by immunohistochemistry. In addition microsatellite instability analysis was performed and the methylation status of the MLH1 promoter was assessed. We then correlated MMR status to clinical outcome. Deficient mismatch repair was found in only 18 (3.5%) out of 515 evaluable patients, of which 13 were caused by hypermethylation of the MLH1 promoter. The median overall survival in proficient MMR (pMMR), dMMR caused by hypermethylation of the MLH1 promoter and total dMMR was 17.9 months (95% confidence interval 16.2–18.8), 7.4 months (95% CI 3.7–16.9) and 10.2 months (95% CI 5.9–19.8), respectively. The disease control rate in pMMR and dMMR patients was 83% (95% CI 79–86%) and 56% (30–80%), respectively. We conclude that dMMR is rare in patients with sporadic advanced CRC. This supports the hypothesis that dMMR tumours have a reduced metastatic potential, as is observed in dMMR patients with early stage disease. The low incidence of dMMR does not allow drawing meaningful conclusions about the outcome of treatment in these patients.
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spelling pubmed-26347182010-01-27 Deficient mismatch repair system in patients with sporadic advanced colorectal cancer Koopman, M Kortman, G A M Mekenkamp, L Ligtenberg, M J L Hoogerbrugge, N Antonini, N F Punt, C J A van Krieken, J H J M Br J Cancer Clinical Study A deficient mismatch repair system (dMMR) is present in 10–20% of patients with sporadic colorectal cancer (CRC) and is associated with a favourable prognosis in early stage disease. Data on patients with advanced disease are scarce. Our aim was to investigate the incidence and outcome of sporadic dMMR in advanced CRC. Data were collected from a phase III study in 820 advanced CRC patients. Expression of mismatch repair proteins was examined by immunohistochemistry. In addition microsatellite instability analysis was performed and the methylation status of the MLH1 promoter was assessed. We then correlated MMR status to clinical outcome. Deficient mismatch repair was found in only 18 (3.5%) out of 515 evaluable patients, of which 13 were caused by hypermethylation of the MLH1 promoter. The median overall survival in proficient MMR (pMMR), dMMR caused by hypermethylation of the MLH1 promoter and total dMMR was 17.9 months (95% confidence interval 16.2–18.8), 7.4 months (95% CI 3.7–16.9) and 10.2 months (95% CI 5.9–19.8), respectively. The disease control rate in pMMR and dMMR patients was 83% (95% CI 79–86%) and 56% (30–80%), respectively. We conclude that dMMR is rare in patients with sporadic advanced CRC. This supports the hypothesis that dMMR tumours have a reduced metastatic potential, as is observed in dMMR patients with early stage disease. The low incidence of dMMR does not allow drawing meaningful conclusions about the outcome of treatment in these patients. Nature Publishing Group 2009-01-27 2009-01-22 /pmc/articles/PMC2634718/ /pubmed/19165197 http://dx.doi.org/10.1038/sj.bjc.6604867 Text en Copyright © 2009 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Clinical Study
Koopman, M
Kortman, G A M
Mekenkamp, L
Ligtenberg, M J L
Hoogerbrugge, N
Antonini, N F
Punt, C J A
van Krieken, J H J M
Deficient mismatch repair system in patients with sporadic advanced colorectal cancer
title Deficient mismatch repair system in patients with sporadic advanced colorectal cancer
title_full Deficient mismatch repair system in patients with sporadic advanced colorectal cancer
title_fullStr Deficient mismatch repair system in patients with sporadic advanced colorectal cancer
title_full_unstemmed Deficient mismatch repair system in patients with sporadic advanced colorectal cancer
title_short Deficient mismatch repair system in patients with sporadic advanced colorectal cancer
title_sort deficient mismatch repair system in patients with sporadic advanced colorectal cancer
topic Clinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2634718/
https://www.ncbi.nlm.nih.gov/pubmed/19165197
http://dx.doi.org/10.1038/sj.bjc.6604867
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