From the Department of Laboratory Medicine and Pathology (Ghosh, Greipp, Knutson, Kloft-Nelson, Mounajjed, Said, Zhang, Kerr, Graham), Mayo Clinic, Rochester, Minnesota.
From the Department of Health Sciences Research (Jenkins), Mayo Clinic, Rochester, Minnesota.
Arch Pathol Lab Med. 2022 Jul 1;146(7):840-845. doi: 10.5858/arpa.2020-0739-OA.
CONTEXT.—: Comprehensive genomic profiling has demonstrated that approximately 20% of pancreatic carcinomas with acinar differentiation harbor potentially targetable BRAF fusions that activate the MAPK pathway.
OBJECTIVES.—: To validate the above finding by BRAF break-apart fluorescence in situ hybridization (FISH) in a large series of pure acinar cell carcinomas (ACCs), evaluate tumors for the presence of BRAF V600E mutations, and compare clinicopathologic features of tumors with BRAF rearrangements with those without.
DESIGN.—: Thirty cases of pure ACC and 6 cases of mixed acinar-neuroendocrine carcinoma (ACC-NEC) were retrieved. A break-apart FISH probe was used to detect BRAF rearrangements. Immunohistochemistry for BRAF V600E was performed.
RESULTS.—: BRAF rearrangements by FISH were found in 6 of 36 cases (17%), 5 of which were pure ACC and 1 was a mixed ACC-NEC. Follow-up was available in 29 of 36 cases (81%). The median survival was 22 months for BRAF-rearranged cases and 16 months for BRAF-intact cases; the 2-year overall survival was 50% for BRAF-rearranged cases and 35% for BRAF-intact cases. No significant clinicopathologic differences were identified in cases with BRAF rearrangement compared with those without BRAF rearrangement. BRAF V600E mutation was identified in 2 of 34 cases (6%), both of which were pure ACC and were BRAF-intact by FISH.
CONCLUSIONS.—: This study supports the finding that BRAF rearrangements are present in approximately 20% of cases and identified BRAF V600E mutations in approximately 5% of cases. These cases may benefit from targeted therapy.
全面基因组分析显示，约 20%具有腺泡分化的胰腺腺癌存在潜在可靶向的 BRAF 融合，激活 MAPK 通路。
通过 BRAF 分离荧光原位杂交（FISH）在大量纯腺泡细胞癌（ACC）中验证上述发现，评估肿瘤中 BRAF V600E 突变的存在情况，并比较具有 BRAF 重排和无 BRAF 重排的肿瘤的临床病理特征。
共检索到 30 例纯 ACC 和 6 例混合腺泡-神经内分泌癌（ACC-NEC）。使用分离 FISH 探针检测 BRAF 重排。进行 BRAF V600E 免疫组化染色。
FISH 检测到 36 例中的 6 例（17%）存在 BRAF 重排，其中 5 例为纯 ACC，1 例为混合 ACC-NEC。29 例（81%）可获得随访资料。BRAF 重排病例的中位生存期为 22 个月，BRAF 完整病例的中位生存期为 16 个月；BRAF 重排病例的 2 年总生存率为 50%，BRAF 完整病例的 2 年总生存率为 35%。与 BRAF 未重排病例相比，BRAF 重排病例的临床病理特征无显著差异。34 例中有 2 例（6%）检测到 BRAF V600E 突变，均为纯 ACC，FISH 结果显示 BRAF 完整。
本研究支持约 20%的病例存在 BRAF 重排，约 5%的病例存在 BRAF V600E 突变的发现。这些病例可能受益于靶向治疗。
