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Heterogenous mismatch-repair status in colorectal cancer

Joost, Patrick LU ; Veurink, Nynke; Holck, Susanne; Klarskov, Louise; Bojesen, Anders; Harbo, Maria; Baldetorp, Bo LU ; Rambech, Eva LU and Nilbert, Mef LU (2014) In Diagnostic Pathology 9.
Abstract
Background: Immunohistochemical staining for mismatch repair proteins is efficient and widely used to identify mismatch repair defective tumors. The tumors typically show uniform and widespread loss of MMR protein staining. We identified and characterized colorectal cancers with alternative, heterogenous mismatch repair protein staining in order to delineate expression patterns and underlying mechanisms. Methods: Heterogenous staining patterns that affected at least one of the mismatch repair proteins MLH1, PMS2, MSH2 and MSH6 were identified in 14 colorectal cancers. Based on alternative expression patterns macro-dissected and micro-dissected tumor areas were separately analyzed for microsatellite instability and MLH1 promoter... (More)
Background: Immunohistochemical staining for mismatch repair proteins is efficient and widely used to identify mismatch repair defective tumors. The tumors typically show uniform and widespread loss of MMR protein staining. We identified and characterized colorectal cancers with alternative, heterogenous mismatch repair protein staining in order to delineate expression patterns and underlying mechanisms. Methods: Heterogenous staining patterns that affected at least one of the mismatch repair proteins MLH1, PMS2, MSH2 and MSH6 were identified in 14 colorectal cancers. Based on alternative expression patterns macro-dissected and micro-dissected tumor areas were separately analyzed for microsatellite instability and MLH1 promoter methylation. Results: Heterogenous retained/lost mismatch repair protein expression could be classified as intraglandular (within or in-between glandular formations), clonal (in whole glands or groups of glands) and compartmental (in larger tumor areas/compartments or in between different tumor blocks). These patterns coexisted in 9/14 tumors and in the majority of the tumors correlated with differences in microsatellite instability/MLH1 methylation status. Conclusions: Heterogenous mismatch repair status can be demonstrated in colorectal cancer. Though rare, attention to this phenomenon is recommended since it corresponds to differences in mismatch repair status that are relevant for correct classification. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1771940323126788 (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Mismatch repair, immunohistochemistry, heterogeneity, MLH1, MSH2, MSH6, PMS2
in
Diagnostic Pathology
volume
9
publisher
BioMed Central
external identifiers
  • wos:000338266000001
  • scopus:84902939693
ISSN
1746-1596
DOI
10.1186/1746-1596-9-126
language
English
LU publication?
yes
id
f24614ba-25c8-47bb-97fd-c53d25e7f425 (old id 4609056)
date added to LUP
2014-09-01 07:38:52
date last changed
2017-04-23 03:52:34
@article{f24614ba-25c8-47bb-97fd-c53d25e7f425,
  abstract     = {Background: Immunohistochemical staining for mismatch repair proteins is efficient and widely used to identify mismatch repair defective tumors. The tumors typically show uniform and widespread loss of MMR protein staining. We identified and characterized colorectal cancers with alternative, heterogenous mismatch repair protein staining in order to delineate expression patterns and underlying mechanisms. Methods: Heterogenous staining patterns that affected at least one of the mismatch repair proteins MLH1, PMS2, MSH2 and MSH6 were identified in 14 colorectal cancers. Based on alternative expression patterns macro-dissected and micro-dissected tumor areas were separately analyzed for microsatellite instability and MLH1 promoter methylation. Results: Heterogenous retained/lost mismatch repair protein expression could be classified as intraglandular (within or in-between glandular formations), clonal (in whole glands or groups of glands) and compartmental (in larger tumor areas/compartments or in between different tumor blocks). These patterns coexisted in 9/14 tumors and in the majority of the tumors correlated with differences in microsatellite instability/MLH1 methylation status. Conclusions: Heterogenous mismatch repair status can be demonstrated in colorectal cancer. Though rare, attention to this phenomenon is recommended since it corresponds to differences in mismatch repair status that are relevant for correct classification. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1771940323126788},
  articleno    = {126},
  author       = {Joost, Patrick and Veurink, Nynke and Holck, Susanne and Klarskov, Louise and Bojesen, Anders and Harbo, Maria and Baldetorp, Bo and Rambech, Eva and Nilbert, Mef},
  issn         = {1746-1596},
  keyword      = {Mismatch repair,immunohistochemistry,heterogeneity,MLH1,MSH2,MSH6,PMS2},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {Diagnostic Pathology},
  title        = {Heterogenous mismatch-repair status in colorectal cancer},
  url          = {http://dx.doi.org/10.1186/1746-1596-9-126},
  volume       = {9},
  year         = {2014},
}