Lack of association between BRAF mutation and MAPK ERK activation in melanocytic nevi

Area of Science:

• Oncology
• Molecular Biology
• Dermatopathology

Background:

• The mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase pathway is frequently activated in melanoma and nevi.
• Mutations in the V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) oncogene are common in melanocytic lesions, correlating with MAPK pathway activation.

Purpose of the Study:

• To investigate the correlation between MAPK activation status, BRAF mutation, and B-Raf expression in common nevi (CN), atypical nevi (AN), and primary cutaneous melanomas (PM).

Main Methods:

• Immunohistochemistry was used to assess phosphorylated (active) MAPK and B-Raf expression in 24 CN, 21 AN, and 26 PM.
• Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was employed to detect BRAF mutations at codon 600.

Main Results:

• Active MAPK was detected in 29% of CN, 48% of AN, and 85% of PM.
• BRAF mutations were found in 67% of CN, 62% of AN, and 58% of PM.
• While 93% of PM with BRAF mutations showed MAPK activation, only 23% of CN and 54% of AN with BRAF mutations did, suggesting BRAF mutation alone is insufficient for MAPK activation in nevi.

Conclusions:

• BRAF mutation is not sufficient for MAPK pathway activation in melanocytic nevi.
• Other events, such as B-Raf overexpression or altered regulation of MAPK pathway components, may be necessary for MAPK activation in these lesions.