Patient characteristics and survival outcomes were gathered through the health record and included age, Breslow thickness, location, decade of diagnosis, histologic type, stage (ie, noninvasive, invasive, or advanced), and follow-up. Pathologic stage 0 was considered noninvasive; stages IA and IB, invasive; and stages IIA or higher, advanced.
Statistical Analysis—Comparisons between the group of patients in the study (n=380) and the group of patients excluded for the reasons stated above (n=258) as well as associations of mutant BRAF status (positive [partial positive and diffuse positive] vs negative) with patient age (young adults [age range, 18–39 years] and middle-aged adults [age range, 40–60 years]), sex, decade of diagnosis, location, histologic type, and stage were evaluated with Wilcoxon rank sum, χ2, Fisher exact, or Cochran-Armitage trend tests. Disease-specific survival and overall survival rates were estimated with the Kaplan-Meier method, and the duration of follow-up was calculated from the date of melanoma diagnosis to the date of death or the last follow-up. Associations of mutant BRAF expression status with death from melanoma and death from any cause were evaluated with Cox proportional hazard regression models and summarized with hazard ratio (HR) and 95% CI. Survival analyses were limited to patients with invasive or advanced disease. Statistical analyses were performed with SAS statistical software (SAS version 9.4). All tests were 2-sided, and P<.05 was considered statistically significant.
Results
Clinical and Tumor Characteristics—Of the 380 tissue specimens that underwent BRAF V600E analysis, 247 had negative staining; 106 had diffuse strong staining; and 27 had focal or partial staining. In total, 133 (35%) were positive, either partially or diffusely. The median age for patients who had negative staining was 45 years; for those with positive staining, it was 41 years (P=.07).
The patients who met inclusion criteria (n=380) were compared with those who were excluded (n=258)(eTable 1). The groups were similar on the basis of sex; age; and melanoma location, stage, and histologic subtype. However, some evidence showed that patients included in the study received the diagnosis of melanoma more recently (1970-1989, 13.2%; 1990-1999, 28.7%; 2000-2009, 58.2%) than those who were excluded (1970-1989, 24.7%; 1990-1999, 23.5%; 2000-2009, 51.8%)(P=.02).
BRAF V600E expression was more commonly found in superficial spreading (37.7%) and nodular melanomas (35.0%) than in situ melanomas (17.1%)(P=.01). Other characteristics of BRAF V600E expression are described in eTable 2. Overall, invasive and advanced melanomas were significantly more likely to harbor BRAF V600E expression than noninvasive melanomas (39.6% and 37.9%, respectively, vs 17.9%; P=.003). However, advanced melanomas more commonly expressed BRAF positivity among women, and invasive melanomas more commonly expressed BRAF positivity among men (eTable 2).
Survival—Survival analyses were limited to 297 patients with confirmed invasive or advanced disease. Of these, 180 (61%) had no BRAF V600E staining; 25 (8%) had partial staining; and 92 (31%) had diffuse positive staining. In total, 117 patients (39%) had a BRAF-mutated melanoma.
Among the patients still alive, the median (interquartile range [IQR]) duration of follow-up was 10.2 (7.0-16.8) years. Thirty-nine patients with invasive or advanced disease had died of any cause at a median (IQR) of 3.0 (1.3-10.2) years after diagnosis. In total, 26 patients died of melanoma at a median (IQR) follow-up of 2.5 (1.3-7.4) years after diagnosis. Eight women and 18 men died of malignant melanoma. Five deaths occurred because of malignant melanoma among patients aged 18 to 39 years, and 21 occurred among patients aged 40 to 60 years. In the 18- to 39-year-old group, all 5 deaths were among patients with a BRAF-positive melanoma. Estimated disease-specific survival rate (95% CI; number still at risk) at 5, 10, 15, and 20 years after diagnosis was 94% (91%-97%; 243), 91% (87%-95%; 142), 89% (85%-94%; 87), and 88% (83%-93%; 45), respectively.