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Defective mismatch-repair in patients with multiple primary tumours including colorectal cancer

Ericson, K LU ; Halvarsson, B LU ; Nagel, J; Rambech, E LU ; Planck, M LU ; Piotrowska, Z; Olsson, H LU and Nilbert, M LU (2003) In European Journal of Cancer 39(2). p.8-240
Abstract

Individuals with an inherited predisposition to cancer development are at an increased risk of developing multiple tumours. Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common hereditary cancer syndromes and is estimated to account for approximately 2% of colorectal cancers. However, HNPCC individuals are at an increased risk of developing other tumour types such as cancers of the endometrium, urothelium and small intestine. We have utilised a population-based regional cancer registry to identify all patients with double primary colorectal cancers and at least one additional malignancy and characterised the tumour spectrum in this patient group. We subsequently selected those 47 individuals who had developed at... (More)

Individuals with an inherited predisposition to cancer development are at an increased risk of developing multiple tumours. Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common hereditary cancer syndromes and is estimated to account for approximately 2% of colorectal cancers. However, HNPCC individuals are at an increased risk of developing other tumour types such as cancers of the endometrium, urothelium and small intestine. We have utilised a population-based regional cancer registry to identify all patients with double primary colorectal cancers and at least one additional malignancy and characterised the tumour spectrum in this patient group. We subsequently selected those 47 individuals who had developed at least four malignancies, including two colorectal cancers, for studies of the tumour characteristics associated with HNPCC. In total, these individuals developed 209 tumours, 156 of which were successfully retrieved. Microsatellite instability (MSI), a phenomenon caused by defective mismatch-repair (MMR), was identified in 63/154 (41%) evaluable tumours with a MSI-high pattern in 59 and a MSI-low pattern in four tumours. All tumours were immunohistochemically stained for the MMR proteins MLH1 and MSH2, with loss of expression in 55/63 (87%) MSI tumours and in 2/89 (2%) microsatellite stable (MSS) tumours. This loss affected MLH1 in 24 tumours and MSH2 in 33 tumours. A concordant loss of expression for the same MMR protein in several tumours from the same individual, a pattern that strongly suggests an underlying germline MMR gene mutation, was found in 17/45 (38%) patients and affected MLH1 in 8 patients and MSH2 in 9 patients. We conclude that the development of multiple primary tumours, including synchronous or metachronous colorectal cancers, is associated with an increased frequency of MSI and loss of immunohistochemical expression of MLH1 and MSH2.

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keywords
Adult, Aged, Aged, 80 and over, Base Pair Mismatch, Colorectal Neoplasms, Female, Humans, Immunohistochemistry, Male, Microsatellite Repeats, Middle Aged, Neoplasm Proteins, Neoplasms, Multiple Primary
in
European Journal of Cancer
volume
39
issue
2
pages
9 pages
publisher
IFAC & Elsevier Ltd.
external identifiers
  • pmid:12509957
  • wos:000181789200025
  • scopus:0037222587
ISSN
1879-0852
DOI
language
English
LU publication?
yes
id
8edcdf2e-64db-43a5-98d3-e95d4472928b (old id 112091)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12509957&dopt=Abstract
date added to LUP
2007-07-18 15:59:58
date last changed
2018-05-29 11:29:32
@article{8edcdf2e-64db-43a5-98d3-e95d4472928b,
  abstract     = {<p>Individuals with an inherited predisposition to cancer development are at an increased risk of developing multiple tumours. Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common hereditary cancer syndromes and is estimated to account for approximately 2% of colorectal cancers. However, HNPCC individuals are at an increased risk of developing other tumour types such as cancers of the endometrium, urothelium and small intestine. We have utilised a population-based regional cancer registry to identify all patients with double primary colorectal cancers and at least one additional malignancy and characterised the tumour spectrum in this patient group. We subsequently selected those 47 individuals who had developed at least four malignancies, including two colorectal cancers, for studies of the tumour characteristics associated with HNPCC. In total, these individuals developed 209 tumours, 156 of which were successfully retrieved. Microsatellite instability (MSI), a phenomenon caused by defective mismatch-repair (MMR), was identified in 63/154 (41%) evaluable tumours with a MSI-high pattern in 59 and a MSI-low pattern in four tumours. All tumours were immunohistochemically stained for the MMR proteins MLH1 and MSH2, with loss of expression in 55/63 (87%) MSI tumours and in 2/89 (2%) microsatellite stable (MSS) tumours. This loss affected MLH1 in 24 tumours and MSH2 in 33 tumours. A concordant loss of expression for the same MMR protein in several tumours from the same individual, a pattern that strongly suggests an underlying germline MMR gene mutation, was found in 17/45 (38%) patients and affected MLH1 in 8 patients and MSH2 in 9 patients. We conclude that the development of multiple primary tumours, including synchronous or metachronous colorectal cancers, is associated with an increased frequency of MSI and loss of immunohistochemical expression of MLH1 and MSH2.</p>},
  author       = {Ericson, K and Halvarsson, B and Nagel, J and Rambech, E and Planck, M and Piotrowska, Z and Olsson, H and Nilbert, M},
  issn         = {1879-0852},
  keyword      = {Adult,Aged,Aged, 80 and over,Base Pair Mismatch,Colorectal Neoplasms,Female,Humans,Immunohistochemistry,Male,Microsatellite Repeats,Middle Aged,Neoplasm Proteins,Neoplasms, Multiple Primary},
  language     = {eng},
  number       = {2},
  pages        = {8--240},
  publisher    = {IFAC & Elsevier Ltd.},
  series       = {European Journal of Cancer},
  title        = {Defective mismatch-repair in patients with multiple primary tumours including colorectal cancer},
  url          = {http://dx.doi.org/},
  volume       = {39},
  year         = {2003},
}