The significance of BRAF V600E mutation status discordance between primary cutaneous melanoma and brain metastases: The implications for BRAF inhibitor therapy.
The significance of BRAF V600E mutation status discordance between primary cutaneous melanoma and brain metastases: The implications for BRAF inhibitor therapy.
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DOI：
10.1097/md.0000000000008404
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发表时间：
2017-12
期刊：
影响因子：
1.6
通讯作者：
Hill ADK
中科院分区：
文献类型：
--
作者：
Hannan EJ;O'Leary DP;MacNally SP;Kay EW;Farrell MA;Morris PG;Power CP;Hill ADK
通过横断面研究比较BRAF V600E在原发性黑色素瘤和脑转移瘤中的状态，以评估不一致性，并评价BRAF抑制剂治疗的临床意义。脑转移在晚期黑色素瘤患者中很常见。40%到60%的黑色素瘤表现出BRAF突变，BRAF V600E是最常见的。选择性BRAF抑制剂治疗已显示出黑色素瘤患者预后的改善。已经证明，并不是所有的转移性病变都具有与原发灶相同的BRAF突变状态，但不一致发生的频率尚不清楚。确定这一点可能对BRAF抑制剂在黑色素瘤脑转移患者中的使用具有指导意义。利用我们当地的组织病理学数据库，对因黑色素瘤脑转移而接受转移切除术的患者进行鉴定。对每个患者的原发灶和转移灶进行组织学回顾，评估BRAF突变状态的不一致性。在7年的时间里，42名患者接受了黑色素瘤原发灶切除后的脑转移切除。中位生存期为9个月。原发灶的中位Breslow厚度为3.4 mm。6名患者(14%)在黑色素瘤原发灶和转移灶的BRAF状态之间存在差异。其中BRAF突变阳性原发转移灶3例，BRAF突变阴性原发转移灶3例，BRAF突变阴性原发转移灶3例。在黑色素瘤原发肿瘤和脑转移瘤的BRAF突变状态中，有一个重要的不符合率。
To compare BRAF V600E status of primary melanoma and brain metastases to assess for discordance by cross-sectional study, and to evaluate clinical implications on BRAF inhibitor therapy. Brain metastases are common in patients with advanced melanoma. Between 40% and 60% of melanomas demonstrate BRAF mutations, BRAF V600E being most common. Selective BRAF inhibitor therapy has shown improvement in outcome in patients with melanoma. It has been demonstrated that not all metastatic lesions carry the same BRAF mutation status as the primary, but the frequency in which discordance occurs remains unclear. Establishing this may have implications in the use of BRAF inhibitors in patients with melanoma brain metastases. Patients who underwent metastectomy for melanoma brain metastases were identified using our local histopathology database. A review of histology of the primary lesion and the metastasis was performed for each patient, assessing for BRAF mutation status discordance. Fourty-two patients who underwent a brain metastectomy following excision of a melanoma primary were identified over a 7-year period. Median survival was 9 months. The median Breslow thickness for the primary lesion was 3.4 mm. Six patients (14%) had discrepancy between the BRAF status of a melanoma primary and metastatic lesion. Of these 6 patients, 3 had a BRAF mutation positive primary with a BRAF mutation negative metastatic lesion, while the other 3 had a BRAF mutation negative primary with BRAF mutation positive metastasis. There is an important discordance rate in the BRAF mutation status of melanoma primaries versus brain metastases.