Identification of HNPCC by Molecular Analysis of Colorectal and Endometrial Tumors

Hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) is a dominantly inherited syndrome characterized by the development of colorectal cancer, endometrial cancer and other cancers and the presence of microsatellite instability (MSI) in tumors. The Bethesda guidelines have been proposed...

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Main Authors:	Vasen, H. F. A., Hendriks, Y., de Jong, A. E., van Puijenbroek, M., Tops, C., Bröcker-Vriends, A. H. J. T., Wijnen, J. Th., Morreau, H.
Format:	Online
Language:	English
Published:	IOS Press 2004
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839268/

id	pubmed-3839268
recordtype	oai_dc
spelling	pubmed-38392682013-12-17 Identification of HNPCC by Molecular Analysis of Colorectal and Endometrial Tumors Vasen, H. F. A. Hendriks, Y. de Jong, A. E. van Puijenbroek, M. Tops, C. Bröcker-Vriends, A. H. J. T. Wijnen, J. Th. Morreau, H. Other Hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) is a dominantly inherited syndrome characterized by the development of colorectal cancer, endometrial cancer and other cancers and the presence of microsatellite instability (MSI) in tumors. The Bethesda guidelines have been proposed for the identification of families suspected of HNPCC that require further molecular analysis. We have evaluated the yield of MSI-analysis in a large series of Dutch families suspected of HNPCC. We also analysed whether the loss of mismatch repair (MMR) protein detected by immunohistochemistry (IHC) of colorectal cancer (CRC) and endometrial cancer correlated with the presence of MSI and/or a MMR gene mutation. The results showed that the Bethesda criteria with a few modifications are appropriate to identify families eligible for genetic testing. In addition, we found that MSI and IHC-analysis of CRC using antibodies against MLH1, MSH2, MSH6 and PMS2 proteins are equally effective for identifying carriers of the known MMR gene defects. However, as long as the role of other putative MMR genes in hereditary CRC has not been elucidated, IHC-analysis cannot completely replace MSI. For this reason, we prefer MSI-analysis as first step in families suspected of HNPCC. On the other hand, in families fulfilling the revised Amsterdam criteria in which the probability of detecting a mutation is relatively high, we would recommend IHC as first diagnostic step because the result might predict the specific underlying MMR gene mutation. MSI or IHC-analysis of endometrial cancer alone was found to be less sensitive compared with these tests performed in colorectal cancer. Therefore, probably the best approach in the analysis of this cancer is to perform both techniques. The identification of HNPCC is important as it makes it possible to target effective preventative measures. Our studies showed that MSI and IHC analysis of colorectal and endometrial cancer, are reliable cost-effective tools that can be used to identify patients with HNPCC. IOS Press 2004 2004-10-29 /pmc/articles/PMC3839268/ /pubmed/15528786 http://dx.doi.org/10.1155/2004/391039 Text en Copyright © 2004 Hindawi Publishing Corporation.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Vasen, H. F. A. Hendriks, Y. de Jong, A. E. van Puijenbroek, M. Tops, C. Bröcker-Vriends, A. H. J. T. Wijnen, J. Th. Morreau, H.
spellingShingle	Vasen, H. F. A. Hendriks, Y. de Jong, A. E. van Puijenbroek, M. Tops, C. Bröcker-Vriends, A. H. J. T. Wijnen, J. Th. Morreau, H. Identification of HNPCC by Molecular Analysis of Colorectal and Endometrial Tumors
author_facet	Vasen, H. F. A. Hendriks, Y. de Jong, A. E. van Puijenbroek, M. Tops, C. Bröcker-Vriends, A. H. J. T. Wijnen, J. Th. Morreau, H.
author_sort	Vasen, H. F. A.
title	Identification of HNPCC by Molecular Analysis of Colorectal and Endometrial Tumors
title_short	Identification of HNPCC by Molecular Analysis of Colorectal and Endometrial Tumors
title_full	Identification of HNPCC by Molecular Analysis of Colorectal and Endometrial Tumors
title_fullStr	Identification of HNPCC by Molecular Analysis of Colorectal and Endometrial Tumors
title_full_unstemmed	Identification of HNPCC by Molecular Analysis of Colorectal and Endometrial Tumors
title_sort	identification of hnpcc by molecular analysis of colorectal and endometrial tumors
description	Hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) is a dominantly inherited syndrome characterized by the development of colorectal cancer, endometrial cancer and other cancers and the presence of microsatellite instability (MSI) in tumors. The Bethesda guidelines have been proposed for the identification of families suspected of HNPCC that require further molecular analysis. We have evaluated the yield of MSI-analysis in a large series of Dutch families suspected of HNPCC. We also analysed whether the loss of mismatch repair (MMR) protein detected by immunohistochemistry (IHC) of colorectal cancer (CRC) and endometrial cancer correlated with the presence of MSI and/or a MMR gene mutation. The results showed that the Bethesda criteria with a few modifications are appropriate to identify families eligible for genetic testing. In addition, we found that MSI and IHC-analysis of CRC using antibodies against MLH1, MSH2, MSH6 and PMS2 proteins are equally effective for identifying carriers of the known MMR gene defects. However, as long as the role of other putative MMR genes in hereditary CRC has not been elucidated, IHC-analysis cannot completely replace MSI. For this reason, we prefer MSI-analysis as first step in families suspected of HNPCC. On the other hand, in families fulfilling the revised Amsterdam criteria in which the probability of detecting a mutation is relatively high, we would recommend IHC as first diagnostic step because the result might predict the specific underlying MMR gene mutation. MSI or IHC-analysis of endometrial cancer alone was found to be less sensitive compared with these tests performed in colorectal cancer. Therefore, probably the best approach in the analysis of this cancer is to perform both techniques. The identification of HNPCC is important as it makes it possible to target effective preventative measures. Our studies showed that MSI and IHC analysis of colorectal and endometrial cancer, are reliable cost-effective tools that can be used to identify patients with HNPCC.
publisher	IOS Press
publishDate	2004
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839268/
_version_	1612030316339265536

Identification of HNPCC by Molecular Analysis of Colorectal and Endometrial Tumors

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