Asano Naofumi, Yoshida Akihiko, Ichikawa Hitoshi, Mori Taisuke, Nakamura Masaya, Kawai Akira, Hiraoka Nobuyoshi
Division of Rare Cancer Research, National Cancer Centre Research Institute, Tokyo, Japan.
Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.
Histopathology. 2017 Feb;70(3):385-393. doi: 10.1111/his.13072. Epub 2016 Nov 10.
The diagnosis of a malignant peripheral nerve sheath tumour (MPNST) can be challenging, as the morphological criteria and existing immunohistochemical markers are not entirely specific. The recent discovery of frequent inactivation of polycomb repressive complex 2 in MPNSTs suggests that immunohistochemical detection of histone 3 trimethylated on lysine 27 (H3K27me3) could be of diagnostic help. This study aimed to clarify the utility of this marker.
We performed immunostaining studies, with monoclonal (C36B11) and polyclonal antibodies in parallel. With the monoclonal antibody, 56% of 54 conventional MPNSTs showed complete loss of staining, whereas 17% showed mosaic loss and 28% showed intact staining. Three MPNSTs showed a novel geographical pattern of complete loss. All three epithelioid MPNSTs retained intact staining. Among 232 non-MPNSTs, only two (0.9%) showed complete loss of staining. Mosaic loss was observed in 38% of non-MPNSTs, whereas the remaining 61% retained intact staining. For conventional MPNSTs, complete loss of H3K27me3 was significantly associated with a higher TNM stage (P = 0.013), a deeper location (P = 0.004), and the presence of heterologous differentiation (P = 0.003). Polyclonal antibodies did not recognize 34% of cases that showed complete loss with the use of monoclonal antibodies.
We confirmed that complete loss of H3K27me3 immunohistochemical staining is moderately sensitive and highly specific for MPNSTs. In contrast to prior studies, we found that mosaic loss of H3K27me3 staining is non-specific, and caution that such a pattern should not be considered to be diagnostic. We recommend the use of a monoclonal antibody to obtain better performance.
恶性外周神经鞘瘤（MPNST）的诊断可能具有挑战性，因为形态学标准和现有的免疫组化标志物并不完全特异。最近发现MPNST中多梳抑制复合物2频繁失活，这表明免疫组化检测赖氨酸27三甲基化的组蛋白3（H3K27me3）可能有助于诊断。本研究旨在阐明该标志物的效用。
我们同时使用单克隆抗体（C36B11）和多克隆抗体进行免疫染色研究。使用单克隆抗体时，54例传统MPNST中有56%显示完全染色缺失，17%显示镶嵌式缺失，28%显示染色完整。3例MPNST显示出一种新的完全缺失的地理模式。所有3例上皮样MPNST均保留完整染色。在232例非MPNST中，只有2例（0.9%）显示完全染色缺失。38%的非MPNST观察到镶嵌式缺失，其余61%保留完整染色。对于传统MPNST，H3K27me3的完全缺失与更高的TNM分期（P = 0.013）、更深的位置（P = 0.004）以及异源性分化的存在（P = 0.003）显著相关。多克隆抗体不能识别使用单克隆抗体时显示完全缺失的34%的病例。
我们证实H3K27me3免疫组化染色的完全缺失对MPNST具有中度敏感性和高度特异性。与先前的研究不同，我们发现H3K27me3染色的镶嵌式缺失是非特异性的，并提醒不应将这种模式视为诊断性的。我们建议使用单克隆抗体以获得更好的性能。
