Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala, Sweden.
Clinical and Experimental Pathology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Acta Oncol. 2020 Jun;59(6):673-680. doi: 10.1080/0284186X.2020.1731924. Epub 2020 Feb 27.
Post-transplant lymphoproliferative disorder (PTLD) is a rare but life-threatening complication of transplantation. For refractory and relapsed PTLD new therapies are needed, such as the antibody-drug conjugate brentuximab vedotin that targets CD30. There is limited knowledge of CD30 expression in various subtypes of PTLD and its correlation to clinicopathological features. Therefore, we studied the expression of CD30 in PTLD following solid organ transplantation and correlated CD30 expression to PTLD subtype, Epstein-Barr virus (EBV)-status, intratumoral regulatory T-cells (Tregs), clinical features, and outcome. We included 50 cases of PTLD from a nation-wide study of PTLDs following solid organ transplantation in Sweden. The tumor biopsies were reevaluated, and clinical data were collected. CD30 expression on tumor cells was analyzed by immunohistochemistry with the clone Ber-H2. Thirty-one cases were stained with clone 236 A/E7 for detection of forkhead box protein 3 (FoxP3, a Treg biomarker). The case series consisted of 6% polymorphic, 88% monomorphic, and 6% Hodgkin lymphoma-like PTLDs and 53% of the cases were EBV+. Overall, 70% (35/50) of the PTLDs were CD30+ (≥1% CD30+ tumor cells) and 30% (15/50) were CD30-. All polymorphic PTLDs ( = 3) and Hodgkin lymphomas ( = 3), 88% (14/16) of non-germinal center type of diffuse large B-cell lymphoma (DLBCL), and 75% (9/12) of T-cell PTLDs were CD30+ whereas all germinal center-type of DLBCL ( = 5) and Burkitt type PTLD ( = 2) were CD30-. CD30+ PTLD tended to be EBV+ more frequently ( = .07) and occurred earlier posttransplant (2.1 vs. 8.2 years, = .01) than CD30- PTLD. Type of transplant and localization of the tumor did not differ between the groups except that CNS engagement was more common in CD30- PTLD ( = .02). CD30-status was not associated with presence of intratumoral Tregs or overall survival. Expression of CD30 varied with PTLD subtype. There was no association between CD30 and survival, regardless of subtype.
移植后淋巴组织增生性疾病（PTLD）是移植的一种罕见但危及生命的并发症。对于难治性和复发性 PTLD，需要新的治疗方法，例如靶向 CD30 的抗体药物偶联物 Brentuximab Vedotin。目前对于各种类型的 PTLD 中 CD30 的表达及其与临床病理特征的相关性知之甚少。因此，我们研究了实体器官移植后 PTLD 中 CD30 的表达，并将 CD30 的表达与 PTLD 亚型、Epstein-Barr 病毒（EBV）状态、肿瘤内调节性 T 细胞（Tregs）、临床特征和结局相关联。我们纳入了瑞典一项实体器官移植后 PTLD 全国性研究中的 50 例 PTLD 病例。对肿瘤活检进行重新评估，并收集临床数据。使用克隆 Ber-H2 通过免疫组织化学分析肿瘤细胞上的 CD30 表达。31 例病例使用克隆 236A/E7 检测叉头框蛋白 3（FoxP3，Treg 标志物）。该病例系列包括 6%多形性、88%单形性和 6%霍奇金淋巴瘤样 PTLD，53%的病例 EBV+。总体而言，70%（50/50）的 PTLD 为 CD30+（≥1%的 CD30+肿瘤细胞），30%（15/50）为 CD30-。所有多形性 PTLD（ = 3）和霍奇金淋巴瘤（ = 3）、非生发中心型弥漫性大 B 细胞淋巴瘤（DLBCL）的 88%（14/16）和 T 细胞 PTLD 的 75%（9/12）为 CD30+，而所有生发中心型 DLBCL（ = 5）和伯基特型 PTLD（ = 2）为 CD30-。CD30+PTLD 倾向于更频繁地 EBV+（ = .07），并且在移植后更早发生（2.1 与 8.2 年， = .01）。CD30- PTLD 的中枢神经系统受累更为常见（ = .02）。移植类型和肿瘤部位在两组之间无差异，除了 CD30- PTLD 中更为常见（ = .02）。CD30 状态与肿瘤内 Tregs 的存在或总生存率无关。CD30 的表达随 PTLD 亚型而变化。无论亚型如何，CD30 与生存率均无关联。
