Trinity College, University of Dublin, Dublin, Ireland.
Oncology Division, The National Children's Research Center, Our Lady's Children's Hospital, Dublin, Ireland.
Pediatr Dev Pathol. 2020 Sep-Oct;23(5):345-351. doi: 10.1177/1093526620910658. Epub 2020 May 4.
The purpose of this study was to establish a reliable panel of antibodies for immunohistochemical corroboration of a diagnosis of clear cell sarcoma of kidney (CCSK), taking into consideration the various genotypic subsets of CCSK.
We conducted full genotypic analysis for evidence of internal tandem duplication (ITD), and in 68 archival cases of CCSK and then immunostained all cases for CCND1, TLE1, and BCOR along with 63 control samples representing tumor types that may enter into the differential diagnosis of CCSK, including 7 congenital mesoblastic nephromas, 2 desmoplastic small round cell tumors, 13 malignant rhabdoid tumors, 9 Ewing sarcomas/primitive neuroectodermal tumor, 5 synovial sarcomas, and 27 Wilms' tumors.
Molecular assays showed that 54 CCSKs harbored a -ITD, 1 case expressed a fusion transcript while none expressed the fusion. The remaining 13 CCSKs were designated "triple-negative" based on the molecular findings. CCND1 showed positive immunoreactivity across all subgroups. TLE1 was positive in 94% of cases, including 1 YWHAE-NUTM2 fusion-positive case. Three -ITD-positive tumors were TLE1-negative. BCOR immunostaining was most variable among subgroups, with triple-negative tumors showing the weakest staining. In all, 10/68 (15%) tumors did not stain for BCOR, of which 4 were triple-negative (4/13 = 31%) and 6 were -ITD-positive (6/54 = 11%). The single -positive tumor showed strong staining for all 3 markers. No single case was negative for all 3 stains; however, 3 cases showed no reactivity for either BCOR or TLE1 of which 1 was triple-negative and 2 -ITD-positive.
Having completed the first comprehensive evaluation of immunostaining of 68 fully genotyped CCSK tumors, we show herein that there is a rationale for the use of a small panel of antibodies to assist in the diagnosis of CCSK regardless of genotype, and we demonstrate that in combination CCND1, TLE1, and BCOR are compelling markers in aiding CCSK diagnosis.
本研究的目的是建立一个可靠的抗体小组，用于免疫组织化学确证肾透明细胞肉瘤（CCSK）的诊断，同时考虑到 CCSK 的各种基因亚型。
我们对 68 例 CCSK 存档病例进行了全面的基因分析，以确定是否存在内部串联重复（ITD），然后对所有病例进行 CCND1、TLE1 和 BCOR 的免疫染色，并对 63 例代表可能进入 CCSK 鉴别诊断的肿瘤类型的对照样本进行免疫染色，包括 7 例先天性中胚层肾瘤、2 例促结缔组织增生性小圆细胞肿瘤、13 例恶性横纹肌样瘤、9 例尤文肉瘤/原始神经外胚层肿瘤、5 例滑膜肉瘤和 27 例肾母细胞瘤。
分子检测显示，54 例 CCSK 存在 ITD，1 例表达融合转录本，而无融合表达。根据分子检测结果，其余 13 例 CCSK 被指定为“三阴性”。CCND1 在所有亚组中均表现出阳性免疫反应。TLE1 在 94%的病例中呈阳性，包括 1 例 YWHAE-NUTM2 融合阳性病例。3 例 ITD 阳性肿瘤 TLE1 阴性。BCOR 免疫染色在亚组之间变化最大，三阴性肿瘤染色最弱。共有 10/68（15%）例肿瘤未染色 BCOR，其中 4 例为三阴性（4/13=31%），6 例为 ITD 阳性（6/54=11%）。单一阳性肿瘤对所有 3 种标志物均表现出强烈的染色。没有任何一种肿瘤 3 种染色均为阴性；然而，有 3 例肿瘤既不表达 BCOR 也不表达 TLE1，其中 1 例为三阴性，2 例为 ITD 阳性。
通过对 68 例完全基因分型的 CCSK 肿瘤进行全面的免疫染色评估，我们证明了使用一小组抗体来协助诊断 CCSK 的合理性，无论基因型如何，并且证明了 CCND1、TLE1 和 BCOR 联合使用是辅助 CCSK 诊断的有力标志物。
