High concordance of BRAF mutational status in matched primary and metastatic melanoma.


Journal

Journal of cutaneous pathology
ISSN: 1600-0560
Titre abrégé: J Cutan Pathol
Pays: United States
ID NLM: 0425124

Informations de publication

Date de publication:
Feb 2019
Historique:
received: 05 07 2018
revised: 31 10 2018
accepted: 11 11 2018
pubmed: 16 11 2018
medline: 11 4 2019
entrez: 16 11 2018
Statut: ppublish

Résumé

Techniques for the accurate identification of activating mutations of BRAF in metastatic melanoma are of great clinical importance, due to the availability of targeted therapies for these tumors. There is uncertainty regarding the frequency with which BRAF status differs between primary and metastatic sites. Between 2011 and 2016, 219 melanoma cases underwent BRAF testing in our institution. In 53 of these cases, paired primary and metastatic specimens were available for polymerase chain reaction (PCR) and immunohistochemical evaluation. Fifty-two out of 53 cases (98%) showed concordant BRAF status between primary and metastatic site by immunohistochemistry (IHC). In one case, a metastasis and its matched primary were positive by IHC, but the metastasis was negative on PCR. On further investigation, PCR was positive in the primary, and repeat PCR in the metastasis was positive, following macrodissection. Our results suggest that discordance of BRAF mutational status between primaries and metastases is a rare occurrence. In one case, IHC provided strong evidence that initial PCR testing had provided a false-negative result due to low tumor volume. Thus, in cases where tissue is difficult to obtain from a metastasis or unavailable, the primary tumor can be used with confidence.

Sections du résumé

BACKGROUND BACKGROUND
Techniques for the accurate identification of activating mutations of BRAF in metastatic melanoma are of great clinical importance, due to the availability of targeted therapies for these tumors. There is uncertainty regarding the frequency with which BRAF status differs between primary and metastatic sites.
METHODS METHODS
Between 2011 and 2016, 219 melanoma cases underwent BRAF testing in our institution. In 53 of these cases, paired primary and metastatic specimens were available for polymerase chain reaction (PCR) and immunohistochemical evaluation.
RESULTS RESULTS
Fifty-two out of 53 cases (98%) showed concordant BRAF status between primary and metastatic site by immunohistochemistry (IHC). In one case, a metastasis and its matched primary were positive by IHC, but the metastasis was negative on PCR. On further investigation, PCR was positive in the primary, and repeat PCR in the metastasis was positive, following macrodissection.
CONCLUSIONS CONCLUSIONS
Our results suggest that discordance of BRAF mutational status between primaries and metastases is a rare occurrence. In one case, IHC provided strong evidence that initial PCR testing had provided a false-negative result due to low tumor volume. Thus, in cases where tissue is difficult to obtain from a metastasis or unavailable, the primary tumor can be used with confidence.

Identifiants

pubmed: 30430609
doi: 10.1111/cup.13393
doi:

Substances chimiques

BRAF protein, human EC 2.7.11.1
Proto-Oncogene Proteins B-raf EC 2.7.11.1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

117-122

Informations de copyright

© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Auteurs

David Cormican (D)

Department of Pathology, Cork University Hospital, Cork, Ireland.
Department of Histopathology, School of Medicine, Trinity College, Dublin, Ireland.

Ciaran Kennedy (C)

Department of Pathology, Cork University Hospital, Cork, Ireland.

Sandra Murphy (S)

Department of Pathology, Cork University Hospital, Cork, Ireland.

Reiltin Werner (R)

Department of Pathology, Cork University Hospital, Cork, Ireland.

Derek G Power (DG)

Department of Medical Oncology, Cork University Hospital, Cork, Ireland.
Department of Medicine, School of Medicine, University College Cork, Cork, Ireland.

Cynthia C B B Heffron (CCBB)

Department of Pathology, Cork University Hospital, Cork, Ireland.
Department of Pathology, School of Medicine, University College Cork, Cork, Ireland.

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