Immunohistochemical staining for p16 and BRAFV600E is useful to distinguish between sporadic and hereditary (Lynch syndrome-related) microsatellite instable colorectal carcinomas

Autor: Hélène Frugier, Florence Boissière-Michot, Frédéric Bibeau, Alexandre Ho-Pun-Cheung, Jacqueline Duffour, Evelyne Lopez-Crapez
Přispěvatelé: Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque
Rok vydání: 2015
Předmět:
0301 basic medicine
MESH: Genes
p16
MESH: Genotype
0302 clinical medicine
MESH: DNA Methylation
MESH: Germ-Line Mutation
Promoter Regions
Genetic
General Medicine
Methylation
MESH: Colorectal Neoplasms
Hereditary Nonpolyposis
Immunohistochemistry
Lynch syndrome
3. Good health
MESH: Staining and Labeling
030220 oncology & carcinogenesis
DNA methylation
DNA mismatch repair
Microsatellite Instability
Proto-Oncogene Proteins B-raf
congenital
hereditary
and neonatal diseases and abnormalities
MESH: Mutation
Genotype
[SDV.CAN]Life Sciences [q-bio]/Cancer
Biology
MLH1
Pathology and Forensic Medicine
03 medical and health sciences
Germline mutation
MESH: Promoter Regions
Genetic
medicine
Humans
Molecular Biology
Genotyping
neoplasms
MSI
Germ-Line Mutation
Surrogate markers
MESH: Proto-Oncogene Proteins B-raf
MESH: Humans
Staining and Labeling
Genes
p16
Microsatellite instability
nutritional and metabolic diseases
MESH: Immunohistochemistry
Cell Biology
DNA Methylation
medicine.disease
Promoter methylation
Molecular biology
Colorectal Neoplasms
Hereditary Nonpolyposis
digestive system diseases
030104 developmental biology
Mutation
Cancer research
MESH: Microsatellite Repeats
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
MESH: Microsatellite Instability
Microsatellite Repeats
Zdroj: Virchows Archiv
Virchows Archiv, Springer Verlag, 2016, 469 (2), pp.135-144. ⟨10.1007/s00428-016-1958-1⟩
ISSN: 1432-2307
0945-6317
DOI: 10.1007/s00428-016-1958-1⟩
Popis: International audience; DNA mismatch repair (MMR) protein analysis by immunohistochemistry (IHC) can identify colorectal cancer (CRC) with microsatellite instability (MSI). As MLH1-deficient CRC can be hereditary or sporadic, markers to distinguish between them are needed. MLH1 promoter methylation assay is the reference method; however, sometimes, it is challenging on formalin-fixed paraffin-embedded tissue samples. We assessed by IHC the expression of BRAFV600E, p16, MGMT, and CDX2 in 55 MLH1-deficient MSI CRC samples (of which 8 had a germline MLH1 mutation) to determine whether this panel differentiates between sporadic and hereditary CRCs. We also analyzed MLH1 promoter methylation by methylation-specific PCR and pyrosequencing and BRAF status by genotyping. None of the hereditary CRCs showed MLH1 methylation, BRAF mutation, BRAFV600E-positive immunostaining, or loss of p16 expression. We detected MLH1 promoter methylation in 67 % and a BRAF mutation in 42 % of CRC, all showing MLH1 promoter methylation. BRAFV600E IHC and BRAF genotyping gave concordant results in all but two samples. Loss of expression of p16 was found in 30 % of CRC with methylation of the MLH1 promoter, but its expression was retained in all non-methylated and part of MLH1-methylated tumors (100 % specificity, 30 % sensitivity). CDX2 and MGMT expression was not associated with MLH1 status. Thus, BRAFV600E and p16 IHC may help in differentiating sporadic from hereditary MLH1-deficient CRC with MSI. Specifically, p16 IHC might be used as a surrogate marker for MLH1 promoter methylation, because all p16-negative CRCs displayed MLH1 methylation, whereas hereditary CRCs were all p16-positive.
Databáze: OpenAIRE
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