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 -