Heterogenous mismatch-repair status in colorectal cancer
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Heterogenous mismatch-repair status in colorectal cancer. / Joost, Patrick; Veurink, Nynke; Holck, Susanne; Klarskov, Louise; Bojesen, Anders; Harbo, Maria; Baldetorp, Bo; Rambech, Eva; Nilbert, Mef.
In: Diagnostic Pathology, Vol. 9, 126, 2014, p. 1-10.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Heterogenous mismatch-repair status in colorectal cancer
AU - Joost, Patrick
AU - Veurink, Nynke
AU - Holck, Susanne
AU - Klarskov, Louise
AU - Bojesen, Anders
AU - Harbo, Maria
AU - Baldetorp, Bo
AU - Rambech, Eva
AU - Nilbert, Mef
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Adaptor Proteins, Signal Transducing
KW - Adenosine Triphosphatases
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Base Pair Mismatch
KW - Colorectal Neoplasms
KW - DNA Methylation
KW - DNA Repair Enzymes
KW - DNA-Binding Proteins
KW - Denmark
KW - Humans
KW - Immunohistochemistry
KW - Male
KW - Microsatellite Instability
KW - Middle Aged
KW - MutS Homolog 2 Protein
KW - Nuclear Proteins
KW - Promoter Regions, Genetic
KW - Sweden
KW - Tumor Markers, Biological
U2 - 10.1186/1746-1596-9-126
DO - 10.1186/1746-1596-9-126
M3 - Journal article
C2 - 24968821
VL - 9
SP - 1
EP - 10
JO - Diagnostic Pathology
JF - Diagnostic Pathology
SN - 1746-1596
M1 - 126
ER -
ID: 138146797