Intra- and Inter-Tumor BRAF Heterogeneity in Acral Melanoma: An Immunohistochemical Analysis

Autor: Yuka Tanaka, Fumitaka Ohno, Yuichi Yamada, Yumiko Kaku-Ito, Maho Murata, Yoshinao Oda, Masutaka Furue, Maiko Wada-Ohno, Takamichi Ito, Toshio Ichiki, Taketoshi Ide, Yuki Kuma
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Pathology
Skin Neoplasms
endocrine system diseases
medicine.disease_cause
law.invention
0302 clinical medicine
law
BRAF
genetics
skin and connective tissue diseases
Melanoma
Spectroscopy
Polymerase chain reaction
Aged
80 and over
Mutation
integumentary system
General Medicine
Middle Aged
Computer Science Applications
Gene Expression Regulation
Neoplastic
030220 oncology & carcinogenesis
immunohistochemistry
Immunohistochemistry
Female
Adult
Proto-Oncogene Proteins B-raf
medicine.medical_specialty
medicine.drug_class
Mutation
Missense
Monoclonal antibody
Sensitivity and Specificity
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
medicine
Humans
Physical and Theoretical Chemistry
gene
Molecular Biology
neoplasms
Aged
Genetic heterogeneity
business.industry
Organic Chemistry
medicine.disease
digestive system diseases
Staining
acral melanoma
enzymes and coenzymes (carbohydrates)
030104 developmental biology
heterogeneity
mutation
business
Immunostaining
Zdroj: International Journal of Molecular Sciences
Volume 20
Issue 24
ISSN: 1422-0067
DOI: 10.3390/ijms20246191
Popis: The current development of BRAF inhibitors has revolutionized the treatment of unresectable melanoma. As the potential heterogeneity of BRAF mutations in melanoma has been reported, accurate detection of BRAF mutations are important. However, the genetic heterogeneity of acral melanoma&mdash
a distinct type of melanoma with a unique genetic background&mdash
has not fully been investigated. We conducted a retrospective review of our acral melanoma patients. Of the 196 patients with acral melanoma, we retrieved 31 pairs of primary and matched metastatic melanomas. We immunostained the 31 pairs with VE1, a BRAFV600E-mutation-specific monoclonal antibody. Immunohistochemistry with VE1 showed a high degree of sensitivity and specificity for detecting BRAFV600E mutations compared with the real-time polymerase chain reaction method. A total of nine primary (29.0%) and eight metastatic (25.8%) acral melanomas were positive for VE1. In three patients (9.7%), we observed a discordance of VE1 staining between the primary and metastatic lesions. Of note, VE1 immunohistochemical staining revealed a remarkable degree of intra-tumor genetic heterogeneity in acral melanoma. Our study reveals that VE1 immunostaining is a useful ancillary method for detecting BRAFV600E mutations in acral melanoma and allows for a clear visualization of intra- and inter-tumor BRAF heterogeneity.
Databáze: OpenAIRE
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