Maya Saroufim1, Robert H Habib1, Rita Gerges1, Jad Saab2, Asif Loya3, Samir S Amr4, Salwa Sheikh5, Mohammad Satti6, Christian Oberkanins7, Ibrahim Khalifeh8. 1. American University of Beirut Medical Center, Beirut, Lebanon. 2. Weill-Cornell Medical Center, New York, NY, United States. 3. Shaukat Khanum Memorial Cancer Centre and Research Hospital, Lahore, Pakistan. 4. King Fahad Specialist Hospital, Dammam, Saudi Arabia. 5. Dhahran Health Center, SAMSO, Dhahran, Saudi Arabia. 6. King Abdul-Aziz Medical City, Jeddah, Saudi Arabia. 7. Weill-Cornell Medical Center, New York, NY, United States; ViennaLab Diagnostics GmbH, Vienna, Austria. 8. American University of Beirut Medical Center, Beirut, Lebanon. Electronic address: ik08@aub.edu.lb.
Abstract
BACKGROUND: Selective BRAF inhibitors have shown dramatic results with regard to improving outcome in patients with melanoma. Testing the BRAF status in matched primary and metastatic melanomas to optimize individual targeted therapy is not well investigated. METHODS: Extended BRAF testing using PCR for 9 mutations and VE1 immunohistochemistry for BRAF V600E detection on 95 lesions including 40 primary melanomas with their matched metastases (n = 42), recurrences (n = 9) and second primaries (n = 4) was performed. Nine patients had multiple metastases. RESULTS: V600E was the only identified mutation type; 35.4% of primary vs. 18.9% of metastatic melanomas. The overall primary-metastatic BRAF status discordance rate was 32.3% using PCR and 27.5% with immunohistochemistry, and was significantly more frequent in primary lesions with mutant BRAF (67%). Males and patients with metastasis to lymph nodes were less likely to be discordant compared to females and those with metastasis to other sites (p = 0.023). Discordant BRAF mutation status was predicted by multivariate binary logistic regression: the presence of a mutant BRAF in the primary melanoma [OR (95% C.I.) = 23.4 (2.4-229.7)] and female gender [OR = 10.6 (1.08-95)]. Inter-metastases BRAF concordance was 100% (6 comparisons). CONCLUSION: A high discordant rate implies the need for clinical trials addressing the response to targeted therapy in patients with discordant BRAF statuses between their primary and metastatic lesions.
BACKGROUND: Selective BRAF inhibitors have shown dramatic results with regard to improving outcome in patients with melanoma. Testing the BRAF status in matched primary and metastatic melanomas to optimize individual targeted therapy is not well investigated. METHODS: Extended BRAF testing using PCR for 9 mutations and VE1 immunohistochemistry for BRAFV600E detection on 95 lesions including 40 primary melanomas with their matched metastases (n = 42), recurrences (n = 9) and second primaries (n = 4) was performed. Nine patients had multiple metastases. RESULTS:V600E was the only identified mutation type; 35.4% of primary vs. 18.9% of metastatic melanomas. The overall primary-metastatic BRAF status discordance rate was 32.3% using PCR and 27.5% with immunohistochemistry, and was significantly more frequent in primary lesions with mutant BRAF (67%). Males and patients with metastasis to lymph nodes were less likely to be discordant compared to females and those with metastasis to other sites (p = 0.023). Discordant BRAF mutation status was predicted by multivariate binary logistic regression: the presence of a mutant BRAF in the primary melanoma [OR (95% C.I.) = 23.4 (2.4-229.7)] and female gender [OR = 10.6 (1.08-95)]. Inter-metastasesBRAF concordance was 100% (6 comparisons). CONCLUSION: A high discordant rate implies the need for clinical trials addressing the response to targeted therapy in patients with discordant BRAF statuses between their primary and metastatic lesions.
Authors: Paul W Sperduto; Wen Jiang; Paul D Brown; Steve Braunstein; Penny Sneed; Daniel A Wattson; Helen A Shih; Ananta Bangdiwala; Ryan Shanley; Natalie A Lockney; Kathryn Beal; Emil Lou; Thomas Amatruda; William A Sperduto; John P Kirkpatrick; Norman Yeh; Laurie E Gaspar; Jason K Molitoris; Laura Masucci; David Roberge; James Yu; Veronica Chiang; Minesh Mehta Journal: Int J Radiat Oncol Biol Phys Date: 2017-03-29 Impact factor: 7.038