Department of Cellular Pathology, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, B15 2GW, UK.
Department of Histopathology, Royal Infirmary of Edinburgh, Edinburgh, EH16 4SA, UK.
Hum Pathol. 2018 Mar;73:144-155. doi: 10.1016/j.humpath.2017.12.007. Epub 2017 Dec 27.
Discussion of liver antibody-mediated rejection during the 2011, 2013, and 2015 Banff liver sessions raised concerns over reliability of complement fragment 4d (C4d) staining, precipitating a global survey followed by a tissue microarray staining quality assessment study among centers on formalin-fixed, paraffin-embedded tissue. Tissue microarray sections containing tissue plugs of resected native and allograft (with acute antibody-mediated rejection) liver, heart, and kidney (n = 33 total cores) were sent to 31 centers for C4d staining using local method(s) and pathologist scoring. Digital whole-slide images (n = 40) were then semiquantitatively scored by 7 experts for background, distribution, and intensity of portal vein and capillary, hepatic artery, sinusoidal, and central vein endothelia and portal and central stromal staining. Results showed that strong and diffuse portal vein and capillary C4d staining, as determined by both local and central pathologists, clearly distinguished allografts showing acute antibody-mediated rejection from native livers and from those with evidence of weaker donor-specific antibody. Downstream vascular endothelial cell C4d staining and assessment were more variable and difficult to identify. C4d staining in the majority of laboratories reliably detects acute liver allograft antibody-mediated rejection in formalin-fixed, paraffin-embedded tissues. Assessment should focus on portal veins and capillaries, sinusoids, and central veins present in peripheral core needle biopsies. C4d staining in one organ does not always translate to staining in another.
讨论 2011 年、2013 年和 2015 年 Banff 肝脏会议期间的肝抗体介导的排斥反应引起了对补体片段 4d（C4d）染色可靠性的关注，随后在全球范围内进行了调查，并在各中心对福尔马林固定、石蜡包埋组织进行了组织微阵列染色质量评估研究。包含切除的天然和同种异体（伴有急性抗体介导的排斥反应）肝脏、心脏和肾脏组织插塞的组织微阵列切片（共 33 个总核）被发送至 31 个中心，使用当地方法（s）和病理学家评分进行 C4d 染色。然后，数字全玻片图像（n = 40）由 7 位专家进行半定量评分，用于评估门静脉和毛细血管、肝动脉、窦状隙和中心静脉内皮以及门和中央基质的背景、分布和强度染色。结果表明，由当地和中心病理学家共同确定的强烈且弥漫的门静脉和毛细血管 C4d 染色，可明确区分显示急性抗体介导排斥反应的同种异体移植物与天然肝脏和有较弱供体特异性抗体证据的肝脏。下游血管内皮细胞 C4d 染色和评估更加多变且难以识别。在大多数实验室中，C4d 染色可可靠地检测福尔马林固定、石蜡包埋组织中的急性肝同种异体移植物抗体介导的排斥反应。评估应集中于在核心针活检中存在的门静脉和毛细血管、窦状隙和中心静脉。一个器官中的 C4d 染色不一定会转化为另一个器官的染色。
