Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.
Histopathology. 2022 Jul;81(1):44-54. doi: 10.1111/his.14639. Epub 2022 May 5.
Dedifferentiated endometrial carcinomas (DDECs)/undifferentiated endometrial carcinomas (UDECs) frequently harbour genomic activation of switch/sucrose non-fermentable (SWI/SNF)-complex proteins, and can show histological overlap with neuroendocrine carcinoma (NEC). The aim of this study was to compare the extent of the expression of neuroendocrine markers, SWI/SNF proteins and mismatch repair (MMR) proteins in DDEC/UDEC and NEC.
The extent of expression of synaptophysin, chromogranin, CD56, ARID1A, ARID1B, SMARCA4, SMARCB1 and MMR proteins was evaluated by immunohistochemistry on 44 SWI/SNF-deficient DDECs/UDECs and 15 NECs. Thirty-three of 44 (75%) DDECs/UDECs showed expression of at least one neuroendocrine marker, with 18 of 44 (41%) expressing two or more neuroendocrine markers, whereas all 15 NECs showed expression of at least one neuroendocrine marker, with 14 of 15 (93%) expressing two or more neuroendocrine markers. Neuroendocrine marker expression in DDECs/UDECs was typically focal when present, with average extents of 17%, 4% and 8% for synaptophysin, chromogranin and CD56 in the positive cases, respectively, in contrast to 73%, 40% and 62% in the positive NEC cases, respectively. All 15 NECs showed intact expression of SWI/SNF-complex proteins, except for one that showed isolated loss of ARID1A. Thirty-eight of 44 DDECs/UDECs were MMR-abnormal (34 with loss of MLH1 and PMS2, and four with loss of PMS2 alone), whereas all NECs retained MMR protein expression.
Our study demonstrates frequent but typically focal neuroendocrine marker expression in SWI/SNF-deficient DDECs/UDECs, whereas NECs typically express two or more neuroendocrine markers, with diffuse expression of at least one marker. ARID1B, SMARCA4 and SMARCB1 immunohistochemistry can be used to aid in the differentiation between DDEC/UDEC and NEC.
去分化子宫内膜癌（DDEC）/未分化子宫内膜癌（UDEC）常伴有 SWI/SNF-复合物蛋白的基因组激活，并且与神经内分泌癌（NEC）具有组织学重叠。本研究旨在比较 DDEC/UDEC 和 NEC 中神经内分泌标志物、SWI/SNF 蛋白和错配修复（MMR）蛋白的表达程度。
通过免疫组织化学法检测 44 例 SWI/SNF 缺陷型 DDEC/UDEC 和 15 例 NEC 中突触素、嗜铬粒蛋白、CD56、ARID1A、ARID1B、SMARCA4、SMARCB1 和 MMR 蛋白的表达程度。44 例 DDEC/UDEC 中有 33 例（75%）至少表达一种神经内分泌标志物，其中 18 例（41%）表达两种或更多种神经内分泌标志物，而 15 例 NEC 均表达至少一种神经内分泌标志物，其中 14 例（93%）表达两种或更多种神经内分泌标志物。存在时，DDEC/UDEC 中的神经内分泌标志物表达通常为局灶性，阳性病例中突触素、嗜铬粒蛋白和 CD56 的平均比例分别为 17%、4%和 8%，而阳性 NEC 病例中的比例分别为 73%、40%和 62%。15 例 NEC 均显示完整的 SWI/SNF 复合物蛋白表达，除了 1 例单独缺失 ARID1A。44 例 DDEC/UDEC 中有 38 例（34 例为 MLH1 和 PMS2 缺失，4 例为 PMS2 单独缺失）为 MMR 异常，而所有 NEC 均保留 MMR 蛋白表达。
本研究表明，SWI/SNF 缺陷型 DDEC/UDEC 中常出现但通常为局灶性的神经内分泌标志物表达，而 NEC 通常表达两种或更多种神经内分泌标志物，至少有一种标志物呈弥漫性表达。ARID1B、SMARCA4 和 SMARCB1 的免疫组织化学可用于辅助 DDEC/UDEC 和 NEC 的鉴别诊断。
