The association between Braf-V600e mutations and death from thin (<=1.0 Mm) melanoma: a population-based nested case-case study from Queensland, Australia

Abstract

Purpose: BRAF mutations are common in cutaneous melanoma but their prognostic significance is unclear, especially for early-stage tumours. We investigated whether BRAF-V600E mutations in thin (≤1.00 mm) melanoma can predict melanoma mortality.Methods: In this REMARK-compliant, nested case-case study, we collected data on a cohort of 27,660 people with a diagnosis of a thin (≤1.00 mm) single locally invasive melanoma between 1995 and 2014 from the population-based Queensland Cancer Registry, Australia. Within this cohort, 436 (1.6%) were fatal ca-ses, i.e. people who had died from their melanoma. We retrieved archival tumours for 85 of these fatal cases which were randomly matched (1:1) with 85 non-fatal cases (melanoma survivors) by age, sex, year of diagnosis, follow-up interval, and tumour thick-ness. BRAF-V600E mutation status in the melanoma tissue was analysed with immunohistochemistry. Using conditional logistic regression, we calculated odds ratios (ORs) for melanoma-specific mortality, adjusting for anatomical location.Results: BRAF-V600E mutations were present in 19 of 85 (22%) fatal cases and 29 of 85 (34%) non-fatal cases. People with BRAF-V600E mutations were more commonly women (52% vs. 17%) and younger (median 52 vs. 65 years) than those with wild-type tumours. Preliminary analyses show that BRAF-V600E mutations were associated with lower melanoma-specific mortality (OR 0.30, 95% CI 0.10–0.89), after adjusting for anatomical site.Conclusions: We found BRAF-V600E mutations to be inversely associated with death from thin (≤1.00 mm) melanoma. Identifica-tion of people with potentially fatal thin melanomas would produce an opportunity to intensify follow-up post-diagnosis