BRAF analysis of primary melanoma tissue samples

BRAF analysis of primary melanoma tissue samples (1)

• do not offer BRAF analysis of melanoma tissue samples from people with stage IA or IB primary melanoma at presentation except as part of a clinical trial
• consider BRAF analysis of melanoma tissue samples from people with stage IIA or IIB primary melanoma
• carry out BRAF analysis of melanoma tissue samples from people with stage IIC to IV primary melanoma
• local skin multidisciplinary teams should arrange BRAF analysis of melanoma tissue samples and state the preferred tissue block for analysis
• when doing BRAF analysis, consider immunohistochemistry as the first test for BRAF V600E, if available
• if BRAF V600E immunohistochemistry is negative or inconclusive, use a different BRAF genetic test
• Offer BRAF analysis of melanoma tissue samples to people with melanoma if they are potential candidates for any ongoing clinical trials that require knowledge of genetic status

Immunohistochemistry (1)

• the 2015 guideline recommended genetic testing for stage IIC and above melanoma. The 2022 committee extended this by recommending that BRAF analysis be considered for stage IIA or IIB melanoma, and carried out for stage IIC to IV melanoma. The committee agreed, based on their experience and in view of advances in targeted treatments since 2015, that early determination of BRAF status has practical utility. They noted that disease relapse occurs in a significant proportion of people with stage IIA to IIC melanoma (up to 50% at 5 years in people with stage IIC melanoma). Knowing BRAF status can speed up decisions about treatment for relapsed melanoma and optimise the use of these newer treatments
• the 2022 committee concluded that immunohistochemistry using BRAF V600E analysis is the most rapid method and enables treatment to be started sooner than is the case with other types of genetic testing
  • also noted evidence that showed BRAF V600E immunohistochemistry rarely produces false positive results. However, some false negative results do occur so the committee agreed that a different BRAF genetic test should be used to double-check a negative or inconclusive result

Notes:

• approximately one-half of advanced (unresectable or metastatic) melanomas harbor a mutation in the BRAF gene, with V600E being the most common mutation (2)
  • targeted therapy with BRAF and MEK inhibitors is associated with significant long-term treatment benefit in patients with BRAF V600-mutated melanoma
  • BRAF encodes a cytoplasmic serine-threonine kinase. More than 97% of BRAF mutations are located in codon 600 of the BRAF gene

Reference:

• NICE (July 2022). Melanoma: assessment and management
• Cheng L, Lopez-Beltran A, Massari F, MacLennan GT, Montironi R. Molecular testing for BRAF mutations to inform melanoma treatment decisions: a move toward precision medicine. Mod Pathol. 2018 Jan;31(1):24-38