| Added by | mollevi |
|---|---|
| Group name | EquipeMY |
| Item Type | Journal Article |
| Title | Immunohistochemical staining for p16 and BRAFV600E is useful to distinguish between sporadic and hereditary (Lynch syndrome-related) microsatellite instable colorectal carcinomas |
| Creator | Boissière-Michot et al. |
| Author | Florence Boissière-Michot |
| Author | Hélène Frugier |
| Author | Alexandre Ho-Pun-Cheung |
| Author | Evelyne Lopez-Crapez |
| Author | Jacqueline Duffour |
| Author | Frédéric Bibeau |
| Abstract | 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. |
| Publication | Virchows Archiv: An International Journal of Pathology |
| Volume | 469 |
| Issue | 2 |
| Pages | 135-144 |
| Date | Aug 2016 |
| Journal Abbr | Virchows Arch. |
| Language | eng |
| DOI | 10.1007/s00428-016-1958-1 |
| ISSN | 1432-2307 |
| Library Catalog | PubMed |
| Extra | PMID: 27220764 |
| Tags | Colorectal Neoplasms, Hereditary Nonpolyposis, DNA Methylation, Genes, p16, Genotype, Germ-Line Mutation, Humans, Immunohistochemistry, Lynch syndrome, Microsatellite Instability, Microsatellite Repeats, MSI, Mutation, original, Promoter methylation, Promoter Regions, Genetic, Proto-Oncogene Proteins B-raf, Staining and Labeling, Surrogate markers |
| Date Added | 2018/11/13 - 17:24:48 |
| Date Modified | 2019/05/21 - 14:38:36 |
Institut de Recherche en Cancérologie de
