Melanocytic nevi excised during B-Raf proto-oncogene (BRAF) inhibitor therapy: A study of 19 lesions from 10 patients - 17/08/15
Abstract |
Background |
There are limited descriptions of histopathology and immune profiles of new or changing melanocytic nevi in the setting of B-Raf proto-oncogene (BRAF) inhibitor therapy.
Objective |
We sought to identify their distinctive features.
Methods |
Clinical charts and histologic review, neuroblastoma RAS viral (v-ras) oncogene homolog genotyping, and immunohistochemistry for HMB-45, BRAFV600E, phosphorylated extracellular signal-regulated kinase (pERK), phosphorylated protein kinase B, CD4, and CD8 were performed on 19 melanocytic nevi from 10 patients and 23 control nevi.
Results |
BRAF inhibitors were administered for metastatic melanoma (7), colonic adenocarcinoma (2), and papillary thyroid carcinoma (1). The average duration of BRAF inhibition before lesion excision was 8 months. Frequently associated histologic features included pigmentation of the stratum corneum, hyperpigmented keratinocytes, dermal melanophages, and deep HMB-45 expression. The lesions were BRAFV600E and neuroblastoma RAS viral (v-ras) oncogene homolog wild-type, expressed diffuse weak-moderate pERK, and possessed a predominance of CD8+ in comparison with CD4+ T lymphocytes within the dermal infiltrates.
Limitation |
This is a retrospective study of a small and heterogeneous group.
Conclusion |
The nevi associated with BRAF inhibitor therapy invariably lack BRAFV600E mutation. BRAF inhibition appears to cause an increased cytotoxic T-cell response and increased mitogen-activated protein kinase activity in BRAF wild-type lesions, supported by pERK expression, possibly resulting in an activated phenotype characterized by increased melanin pigmentation and deep HMB-45 expression.
Le texte complet de cet article est disponible en PDF.Key words : B-Raf proto-oncogene inhibition, CD4, CD8, melanocytic nevi, phosphorylated extracellular signal-regulated kinase, phosphorylated protein kinase B
Abbreviations used : AKT, BRAF, MAPK, NRAS, pAKT, pERK, TIL
Plan
Funding sources: None. |
|
Conflicts of interest: None declared. |
Vol 73 - N° 3
P. 491 - septembre 2015 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?