Interpretation of immunohistochemistry for mismatch repair proteins is only reliable in a specialized setting

Autor: Maria L. Mlynek-Kersjes, Riki W. Willems, Lucia I. H. Overbeek, Hans van der Linden, Nicoline Hoogerbrugge, Joannes H.J.M. Van Krieken, Stefan V. Dubois, Konnie M. Hebeda, Willeke A. M. Blokx, Marjolijn J. L. Ligtenberg, Rosella P.M.G. Hermens, Jos W. R. Meijer
Rok vydání: 2008
Předmět:
Pathology
Genetics and epigenetic pathways of disease [NCMLS 6]
DNA Mismatch Repair
Germany
PMS2
Molecular diagnosis
prognosis and monitoring [UMCN 1.2]
Mismatch Repair Endonuclease PMS2
Netherlands
Chronic inflammation and autoimmunity [UMCN 4.2]
Adenosine Triphosphatases
Observer Variation
Nuclear Proteins
Immunohistochemistry
Lynch syndrome
DNA-Binding Proteins
Gene Expression Regulation
Neoplastic
MutS Homolog 2 Protein
Microsatellite Instability
Anatomy
Colorectal Neoplasms
MutL Protein Homolog 1
medicine.medical_specialty
Age-related aspects of cancer [ONCOL 2]
Implementation Science [NCEBP 3]
MLH1
Pathology and Forensic Medicine
Quality of Care [ONCOL 4]
Genomic disorders and inherited multi-system disorders [IGMD 3]
Molecular epidemiology [NCEBP 1]
Translational research [ONCOL 3]
Predictive Value of Tests
medicine
Humans
Adaptor Proteins
Signal Transducing
Hereditary cancer and cancer-related syndromes [ONCOL 1]
business.industry
Microsatellite instability
Cancer
Reproducibility of Results
medicine.disease
Colorectal Neoplasms
Hereditary Nonpolyposis
digestive system diseases
MSH6
Quality of Care [EBP 4]
Tumor microenvironment [UMCN 1.3]
Human Reproduction [NCEBP 12]
DNA Repair Enzymes
MSH2
Surgery
Microsatellite Instability Analysis
business
Quality of hospital and integrated care [NCEBP 4]
Immunity
infection and tissue repair [NCMLS 1]
Zdroj: ResearcherID
American Journal of Surgical Pathology, 32, 8, pp. 1246-51
American Journal of Surgical Pathology, 32, 1246-51
ISSN: 1532-0979
0147-5185
Popis: Contains fulltext : 69655.pdf (Publisher’s version ) (Closed access) We examined the validity of immunohistochemistry for mismatch repair (MMR) proteins in colorectal cancer specimens to identify patients at risk for Lynch syndrome (hereditary nonpolyposis colorectal cancer) and patients with sporadic microsatellite instable colorectal cancer. This was assessed by observer agreement for and accuracy of interpretation of immunohistochemistry. Seven pathologists from 5 different pathology laboratories evaluated 100 molecularly defined colorectal cancers stained for MLH1, PMS2, MSH2, and MSH6. Two of the pathologists were experienced in interpretation of immunohistochemistry for MMR proteins. After evaluation of a subset of 20 cases, a discussion meeting was organized, after which pathologists evaluated all 100 cases. Staining patterns were interpreted as aberrant, normal, or indefinite. In 82% of tumors, 5 or more pathologists reached the same interpretation, which was considered the consensus diagnosis. Consensus was reached slightly less frequently in microsatellite instable than in stable tumors, and interobserver variation was moderate to substantial (kappa: 0.49-0.79). More microsatellite instable tumors showed an indefinite staining pattern compared with microsatellite stable tumors. Three out of 7 pathologists, including the 2 experienced pathologists, did not miss a microsatellite instable tumor. Each pathologist found at least 1 tumor with an aberrant staining pattern, whereas consensus was a normal staining pattern and the tumor was microsatellite stable. We conclude that, if restricted to experienced pathologists, immunohistochemistry is a valid tool to identify patients at risk for Lynch syndrome and patients with sporadic microsatellite instable colorectal cancer. An indefinite or aberrant staining result has to be followed by molecular microsatellite instability analysis to confirm the presence of a defective DNA MMR system.
Databáze: OpenAIRE
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