Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea.
J Oral Pathol Med. 2021 Jan;50(1):85-91. doi: 10.1111/jop.13108. Epub 2020 Oct 9.
Although immunohistochemistry (IHC) along with molecular tests has been investigated in ameloblastoma for BRAF V600E detection, VE1 IHC has not been studied in odontogenic carcinomas (OCs) and benign mixed epithelial and mesenchymal odontogenic tumours (BMOTs). Here, we performed BRAF V600E mutation analysis, examined the expression pattern of VE1 IHC, and comparatively evaluated the performance of two VE1 antibodies in ameloblastomas, OCs and BMOTs.
BRAF V600E detection was performed using Sanger sequencing in a total of 47 odontogenic tumours: 28 ameloblastomas, 6 OCs and 13 BMOTs. VE1 IHC was conducted using two different antibodies (IHC-A and IHC-V), and their performance was analysed by calculating the sensitivity and specificity compared with sequencing.
BRAF V600E mutations were identified in 24/28 (85.7%) ameloblastomas, 2/5 (40.0%) ameloblastic carcinomas (ACs), 3/7 (42.9%) ameloblastic fibromas and 1/2 (50.0%) ameloblastic fibro-odontomas. In the presence of the mutation, VE1 showed diffuse cytoplasmic staining in ameloblastomas and ACs, whereas all BMOTs were negative for VE1. IHC-A and IHC-V yielded a sensitivity of 76.7% and 60.0%, respectively, although both antibodies showed 100% specificity.
OCs and BMOTs have BRAF V600E mutations in common at lower frequencies than ameloblastoma. Diffuse VE1 cytoplasmic staining in AC suggests the utility of MAPK-targeted therapy as selectively applied in ameloblastoma, and consistent VE1 false-negative expression in BMOTs requires further investigation. Considering the high specificity but low sensitivity of VE1 IHC, molecular tests should be performed to determine the presence of BRAF V600E mutations in odontogenic tumours.
虽然免疫组织化学（IHC）结合分子检测已在造釉细胞瘤中用于检测 BRAF V600E，但 VE1 IHC 尚未在牙源性癌（OCs）和良性混合上皮和间充质牙源性肿瘤（BMOTs）中进行研究。在这里，我们进行了 BRAF V600E 突变分析，检查了 VE1 IHC 的表达模式，并比较评估了两种 VE1 抗体在造釉细胞瘤、OCs 和 BMOTs 中的性能。
对总共 47 个牙源性肿瘤进行了 BRAF V600E 检测：28 个造釉细胞瘤、6 个 OCs 和 13 个 BMOTs。使用两种不同的抗体（IHC-A 和 IHC-V）进行 VE1 IHC，并通过计算与测序相比的敏感性和特异性来分析其性能。
在 28 个造釉细胞瘤、5 个造釉细胞癌（ACs）、7 个造釉细胞瘤中的 3 个和 2 个造釉细胞瘤中的 1 个中发现了 BRAF V600E 突变纤维瘤和 2 个造釉细胞瘤纤维-成釉细胞瘤。在存在突变的情况下，VE1 在造釉细胞瘤和 AC 中显示弥漫的细胞质染色，而所有 BMOTs 均为 VE1 阴性。IHC-A 和 IHC-V 的敏感性分别为 76.7%和 60.0%，尽管两种抗体均显示 100%特异性。
OCs 和 BMOTs 与造釉细胞瘤一样，BRAF V600E 突变的频率较低。AC 中弥漫的 VE1 细胞质染色提示 MAPK 靶向治疗的应用具有选择性，而 BMOTs 中一致的 VE1 假阴性表达需要进一步研究。考虑到 VE1 IHC 的高特异性但低敏感性，应进行分子检测以确定牙源性肿瘤中 BRAF V600E 突变的存在。
