Heterogenous mismatch-repair status in colorectal cancer
Author
Summary, in English
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
Department/s
- Breastcancer-genetics
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- EpiHealth: Epidemiology for Health
Publishing year
2014
Language
English
Publication/Series
Diagnostic Pathology
Volume
9
Full text
Document type
Journal article
Publisher
BioMed Central (BMC)
Topic
- Cancer and Oncology
Keywords
- Mismatch repair
- immunohistochemistry
- heterogeneity
- MLH1
- MSH2
- MSH6
- PMS2
Status
Published
ISBN/ISSN/Other
- ISSN: 1746-1596