Positive BRAF Variant Expression is Associated With Improved Melanoma Prognosis

Positive BRAF V600E expression is significantly associated with nonrecurrent disease and better survival in patients with superficial spreading melanomas (SSMs), according to study results published in Dermatology.

Researchers conducted a retrospective review of melanoma cases recorded in the Danish Pathology Register between 1995 and 2015. Clinical and histopathological data were retrieved for each case. Melanoma-specific and disease-free survival rates were calculated using data from medical records, which were followed until death or October 1, 2020. Intratumor heterogeneity was also assessed using a combination of immunohistochemistry and mRNA analysis.

Samples from 166 (mean age, 57.7 years: 51.8% men) participants with SSMs were included in the study. The most common tumor site was the trunk (50.0%) or leg (24.7%). The majority of participants had localized disease, although 22.9% had at least 1 lymph node metastasis.

The median follow-up period for survival was 121 months. During the follow-up period, 40 (24.1%) participants experienced disease recurrence and 30 (18.1%) died of melanoma. Of the 166 cases, 85 (51.2%) were positive for BRAF V600E  antibodies. Expression of BRAF V600E was homogenous throughout each of the BRAF-positive melanomas. The presence of the BRAF V600E gene did not appear to result in increased transcription of BRAF mRNA compared with BRAF V600E-negative tumors.

Expression of BRAF V600E was associated with significantly lower recurrence rates — the 5-year melanoma-specific survival rate was 92% among those with BRAF V600E-positive tumors vs 82% among those with BRAF V600E-negative tumors (P =.0041). Participants with BRAF V600E-positive tumors also had improved 5-year disease-free survival rates (89% vs 69%; P =.0021). In multivariable models, presence of tumor-infiltrating lymphocytes, sentinel lymph node biopsy negativity, and low Breslow thickness were observed to be independent predictors of better prognosis.

Study limitations include the lack of generalizability due to the homogenous study cohort.

Researchers conclude, “[W]e have shown that BRAF V600E is expressed homogenously throughout the individual SMM tumors and the mutation does not result in an increased transcription, as measured by mRNA levels.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.