BRAF testing modalities in histiocytic disorders : Comparative analysis and proposed testing algorithm
© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..
OBJECTIVES: Understanding of histiocytic disorders has been revolutionized by demonstration of mitogen-activated protein kinase (MAPK) pathway mutations, most commonly BRAFV600E. The optimal testing strategy to assess BRAFV600E is unknown. We aimed to compare performance of testing modalities, to propose a framework for evaluation of BRAFV600E mutation status in histiocytic disorders.
METHODS: We retrospectively reviewed patients with histiocytic disorders and BRAF mutation testing on a lesional tissue specimen.
RESULTS: In 120 patients, BRAF assessment included immunohistochemistry (IHC) in 97 (80.2%), polymerase chain reaction (PCR) in 35 (28.9%), and next-generation sequencing (NGS) in 62 (51.2%). Forty-five underwent both NGS and IHC. With NGS as the gold standard, the sensitivity and specificity of IHC were 82.4% and 96.4%. Three false negatives were observed in biopsy specimens with low BRAFV600E variant allele frequency or decalcified tissue. One false-positive IHC was observed in a lung biopsy specimen, likely due to antibody cross-reactivity with respiratory cilia. Among 14 with successful NGS and PCR, a single discordance was observed. Two PCR-to-IHC discrepancies were observed, including one other false-positive IHC.
CONCLUSIONS: Immunohistochemistry was highly specific for detection of BRAFV600E. Main caveats were false negatives and lack of detection of non-BRAFV600E mutations. We propose the use of IHC as initial screening in general practice with reflex molecular testing if negative.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:160 |
|---|---|
| Enthalten in: |
American journal of clinical pathology - 160(2023), 5 vom: 02. Nov., Seite 483-489 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Acosta-Medina, Aldo A [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
BRAF kinase |
|---|
| Anmerkungen: |
Date Completed 08.11.2023 Date Revised 14.11.2023 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1093/ajcp/aqad076 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM359589480 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM359589480 | ||
| 003 | DE-627 | ||
| 005 | 20231226081212.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1093/ajcp/aqad076 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1198.xml |
| 035 | |a (DE-627)NLM359589480 | ||
| 035 | |a (NLM)37458275 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Acosta-Medina, Aldo A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a BRAF testing modalities in histiocytic disorders |b Comparative analysis and proposed testing algorithm |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 08.11.2023 | ||
| 500 | |a Date Revised 14.11.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com. | ||
| 520 | |a OBJECTIVES: Understanding of histiocytic disorders has been revolutionized by demonstration of mitogen-activated protein kinase (MAPK) pathway mutations, most commonly BRAFV600E. The optimal testing strategy to assess BRAFV600E is unknown. We aimed to compare performance of testing modalities, to propose a framework for evaluation of BRAFV600E mutation status in histiocytic disorders | ||
| 520 | |a METHODS: We retrospectively reviewed patients with histiocytic disorders and BRAF mutation testing on a lesional tissue specimen | ||
| 520 | |a RESULTS: In 120 patients, BRAF assessment included immunohistochemistry (IHC) in 97 (80.2%), polymerase chain reaction (PCR) in 35 (28.9%), and next-generation sequencing (NGS) in 62 (51.2%). Forty-five underwent both NGS and IHC. With NGS as the gold standard, the sensitivity and specificity of IHC were 82.4% and 96.4%. Three false negatives were observed in biopsy specimens with low BRAFV600E variant allele frequency or decalcified tissue. One false-positive IHC was observed in a lung biopsy specimen, likely due to antibody cross-reactivity with respiratory cilia. Among 14 with successful NGS and PCR, a single discordance was observed. Two PCR-to-IHC discrepancies were observed, including one other false-positive IHC | ||
| 520 | |a CONCLUSIONS: Immunohistochemistry was highly specific for detection of BRAFV600E. Main caveats were false negatives and lack of detection of non-BRAFV600E mutations. We propose the use of IHC as initial screening in general practice with reflex molecular testing if negative | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a BRAF kinase | |
| 650 | 4 | |a clinical pathology | |
| 650 | 4 | |a histiocytosis | |
| 650 | 4 | |a immunohistochemistry | |
| 650 | 4 | |a sequence analysis | |
| 650 | 7 | |a Proto-Oncogene Proteins B-raf |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a BRAF protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 700 | 1 | |a Abeykoon, Jithma P |e verfasserin |4 aut | |
| 700 | 1 | |a Go, Ronald S |e verfasserin |4 aut | |
| 700 | 1 | |a Goyal, Gaurav |e verfasserin |4 aut | |
| 700 | 1 | |a Ravindran, Aishwarya |e verfasserin |4 aut | |
| 700 | 1 | |a Schram, Susan M |e verfasserin |4 aut | |
| 700 | 1 | |a Rech, Karen L |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t American journal of clinical pathology |d 1945 |g 160(2023), 5 vom: 02. Nov., Seite 483-489 |w (DE-627)NLM000037001 |x 1943-7722 |7 nnns |
| 773 | 1 | 8 | |g volume:160 |g year:2023 |g number:5 |g day:02 |g month:11 |g pages:483-489 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1093/ajcp/aqad076 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 160 |j 2023 |e 5 |b 02 |c 11 |h 483-489 | ||