Comparing BRAF Mutation Status in Corresponding Primary and Metastatic Cutaneous Melanomas: Implications on Optimized Targeted Therapy
Maya Saroufim, Robert Habib, Rita Gerges, Jad Saab, Asif Loya, Salwa Sheikh, Mohamed Satti, Christian Oberkanins, Ibrahim Khalifeh. American University of Beirut Medical Center, Beirut, Lebanon; ViennaLab Diagnostics GmbH, Vienna, Austria; Weill-Cornell Medical Center, New York, NY; Shaukat Khanum Memorial Cancer Center and Research Hospital, Lahore, Pakistan; Dhahran Health Center, SAMSO, Dhahran, Saudi Arabia; King Abdulaziz Medical City, Jeddah, Saudi Arabia
Background: Selective oral BRAF inhibitors show promising results in the treatment of metastatic melanomas. Consequently, this mandates checking the concordance of BRAF status in primary (PM) and metastatic (MM) melanomas to optimize individual targeted therapy.
Design: Extended BRAF testing for 9 mutations on 95 lesions from 40 patients (men/women: 27/13; age= 59±13 years) including 40 PM with their corresponding MM (n=42), recurrences (n=9) and second primaries (n=4) was performed. Multiple metastatic sites were present in 9 patients [2 sites (n=6), 3 sites (n=2) and 4 sites (n=1)].
Results: BRAF mutation status was obtained for 85/95 (89.5%) lesions. V600E was the only identified mutation type documented in 35.4% of PM vs. 18.9% of MM. The overall PM-MM BRAF status discordance rate was 32.3% (11/34), and this was significantly more frequent in PM with mutant BRAF (8/12; 67%) versus PM with wild-type BRAF (3/22; 14%, p=0.005) Patients with metastasis to lymph nodes (3/20; 15%) were less likely to be discordant compared to those with metastasis to other sites (8/14; 57.1%, p=0.023). Females (7/13; 53.8%) were more likely to have discordant PM-MM BRAF status than males (4/21; 19%, p=0.06). Patient age was similar in patients with concordant and discordant BRAF status (58±13 vs. 62±14 years; p=0.41). PM anatomic location (p=0.23) and time-to-metastasis (p=0.55) were also unrelated to PM-MM BRAF mutation discordance. Discordant BRAF mutation status was predicted by multivariate binary logistic regression: 1) the presence of a mutant BRAF in PM [OR (95% C.I.) = 23.4 (2.4-229.7)] and 2) male gender [OR = 0.094 (0.01-0.93)]. MM-MM BRAF concordance was available for 6 possible comparisons and displayed a 100% concordance rate.
Conclusions: A high discordant rate implies the need for re-testing of the MM before initiation of BRAF targeted therapy. High MM-MM concordance advocates that testing the most accessible metastatic site is sufficient to obtain accurate BRAF mutation status.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 34, Tuesday Morning