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Phenotypic heterogeneity in hereditary nonpolyposis colorectal cancer: identical germline mutations associated with variable tumor morphology and immunohistochemical expression.

Halvarsson, Britta LU ; Müller, Wolfram; Planck, Maria LU ; Benoni, Anna-Clara LU ; Mangell, Peter LU ; Ottosson, Johan; Hallén, Magnus LU ; Isinger Ekstrand, Anna LU and Nilbert, Mef LU (2007) In Journal of Clinical Pathology 60(7). p.781-786
Abstract
BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is associated with high risks for colorectal and endometrial cancer, young age at onset and an increased risk of multiple primary tumours. Colorectal cancer in HNPCC is characterised by poor tumour differentiation, an expanding growth pattern, and a pronounced lymphocytic reaction with tumour-infiltrating lymphocytes. Aims and METHODS: The mutation spectrum in HNPCC is diverse and in order to clarify whether the HNPCC tumour phenotype is influenced by the underlying genetic alteration, 29 colorectal cancers and 12 adenomas from 24 individuals in two HNPCC families were morphologically and immunohistochemically characterised. RESULTS: The tumour morphology as well as the... (More)
BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is associated with high risks for colorectal and endometrial cancer, young age at onset and an increased risk of multiple primary tumours. Colorectal cancer in HNPCC is characterised by poor tumour differentiation, an expanding growth pattern, and a pronounced lymphocytic reaction with tumour-infiltrating lymphocytes. Aims and METHODS: The mutation spectrum in HNPCC is diverse and in order to clarify whether the HNPCC tumour phenotype is influenced by the underlying genetic alteration, 29 colorectal cancers and 12 adenomas from 24 individuals in two HNPCC families were morphologically and immunohistochemically characterised. RESULTS: The tumour morphology as well as the immunohistochemical expression of beta-catenin varied extensively within the families as well as between synchronous/metachronous colorectal cancers from the same individual. Poor tumour differentiation, an expanding growth pattern, and tumour-infiltrating lymphocytes occurred at higher frequencies in proximal tumours, whereas distal colorectal cancers often lacked distinct HNPCC-associated morphological features. CONCLUSIONS: The clinical, morphological and immunohistochemical variability observed within these families indicates that other mechanisms than the underlying germline mutation influence the HNPCC phenotype. Since morphological features linked to HNPCC are less frequent in distal cancers, it may be particularly relevant to obtain family history and age of onset in these tumours in order to identify individuals with HNPCC. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
HNPCC, histopathology, hereditary non-polyposis colorectal cancer, heterogeneity, MMR, mismatch-repair
in
Journal of Clinical Pathology
volume
60
issue
7
pages
781 - 786
publisher
BMJ Publishing Group
external identifiers
  • wos:000247592300008
  • scopus:34447322031
ISSN
1472-4146
DOI
10.1136/jcp.2006.040402
language
English
LU publication?
yes
id
b2a7d7b5-375c-47fd-8f22-db41679d96d3 (old id 160139)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16901974&dopt=Abstract
date added to LUP
2007-07-12 15:42:43
date last changed
2017-08-27 05:14:29
@article{b2a7d7b5-375c-47fd-8f22-db41679d96d3,
  abstract     = {BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is associated with high risks for colorectal and endometrial cancer, young age at onset and an increased risk of multiple primary tumours. Colorectal cancer in HNPCC is characterised by poor tumour differentiation, an expanding growth pattern, and a pronounced lymphocytic reaction with tumour-infiltrating lymphocytes. Aims and METHODS: The mutation spectrum in HNPCC is diverse and in order to clarify whether the HNPCC tumour phenotype is influenced by the underlying genetic alteration, 29 colorectal cancers and 12 adenomas from 24 individuals in two HNPCC families were morphologically and immunohistochemically characterised. RESULTS: The tumour morphology as well as the immunohistochemical expression of beta-catenin varied extensively within the families as well as between synchronous/metachronous colorectal cancers from the same individual. Poor tumour differentiation, an expanding growth pattern, and tumour-infiltrating lymphocytes occurred at higher frequencies in proximal tumours, whereas distal colorectal cancers often lacked distinct HNPCC-associated morphological features. CONCLUSIONS: The clinical, morphological and immunohistochemical variability observed within these families indicates that other mechanisms than the underlying germline mutation influence the HNPCC phenotype. Since morphological features linked to HNPCC are less frequent in distal cancers, it may be particularly relevant to obtain family history and age of onset in these tumours in order to identify individuals with HNPCC.},
  author       = {Halvarsson, Britta and Müller, Wolfram and Planck, Maria and Benoni, Anna-Clara and Mangell, Peter and Ottosson, Johan and Hallén, Magnus and Isinger Ekstrand, Anna and Nilbert, Mef},
  issn         = {1472-4146},
  keyword      = {HNPCC,histopathology,hereditary non-polyposis colorectal cancer,heterogeneity,MMR,mismatch-repair},
  language     = {eng},
  number       = {7},
  pages        = {781--786},
  publisher    = {BMJ Publishing Group},
  series       = {Journal of Clinical Pathology},
  title        = {Phenotypic heterogeneity in hereditary nonpolyposis colorectal cancer: identical germline mutations associated with variable tumor morphology and immunohistochemical expression.},
  url          = {http://dx.doi.org/10.1136/jcp.2006.040402},
  volume       = {60},
  year         = {2007},
}