Agaimy Abbas, Bertz Simone, Cheng Liang, Hes Ondrej, Junker Kerstin, Keck Bastian, Lopez-Beltran Antonio, Stöckle Michael, Wullich Bernd, Hartmann Arndt
Institute of Pathology, University Hospital of Erlangen, Krankenhausstrasse 8-10, 91054, Erlangen, Germany.
Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Virchows Arch. 2016 Sep;469(3):321-30. doi: 10.1007/s00428-016-1977-y. Epub 2016 Jun 23.
Loss of the SWI/SNF chromatin remodeling complex has been recently implicated in the pathogenesis of dedifferentiated carcinomas from different organs, but its possible role in undifferentiated urothelial carcinoma (UC) has not been studied to date. In this study, we analyzed by immunohistochemistry 14 undifferentiated UCs (11 from bladder and 3 from renal pelvis) with a nondescript anaplastic or rhabdoid morphology, using commercially available antibodies against the SWI/SNF components SMARCB1 (INI1), SMARCA2, SMARCA4, SMARCC1, SMARCC2, and ARID1A. Patients were eight females and six males aged 40 to 84 years (median, 65). All tumors were muscle-invasive (9 were T3-4). A conventional UC component was seen in eight cases and varied from in situ to papillary. The undifferentiated component comprised 60-100 % of the tumors. Histologically, most tumors showed diffuse dyscohesive or pseudoalveolar growth of variably sized cells with frequent rhabdoid features. Transition from conventional to undifferentiated UC was abrupt, except in one case. The undifferentiated component almost always expressed pan-cytokeratin AE1/AE3 (13/14) and variably vimentin (8/14) and GATA3 (9/14). Complete loss of at least one SWI/SNF subunit limited to the undifferentiated component was detected in 10/14 cases (71 %). SMARCA2 was most frequently lost (six) followed by ARID1A (four), SMARCB1/INI1 (two), SMARCA4 (one), and SMARCC1 (one). This is the first study exploring SWI/SNF expression in undifferentiated UC of the urinary tract. Our results are in line with recent studies reporting involvement of the SWI/SNF complex in the dedifferentiation process of a variety of epithelial neoplasms in different organs, including the urinary tract, and association with aggressive clinical course.
SWI/SNF染色质重塑复合体的缺失最近被认为与不同器官去分化癌的发病机制有关，但迄今为止其在未分化尿路上皮癌（UC）中的可能作用尚未得到研究。在本研究中，我们使用针对SWI/SNF成分SMARCB1（INI1）、SMARCA2、SMARCA4、SMARCC1、SMARCC2和ARID1A的市售抗体，通过免疫组织化学分析了14例具有难以描述的间变或横纹肌样形态的未分化UC（11例来自膀胱，3例来自肾盂）。患者为8名女性和6名男性，年龄40至84岁（中位数为65岁）。所有肿瘤均为肌层浸润性（9例为T3-4期）。8例可见传统UC成分，范围从原位癌到乳头状癌。未分化成分占肿瘤的60%-100%。组织学上，大多数肿瘤表现为大小不一的细胞弥漫性离散或假腺泡样生长，常有横纹肌样特征。除1例病例外，从传统UC到未分化UC的转变是突然的。未分化成分几乎总是表达泛细胞角蛋白AE1/AE3（13/14），可变表达波形蛋白（8/14）和GATA3（9/14）。10/14例（71%）检测到至少一种SWI/SNF亚基在未分化成分中完全缺失。SMARCA2缺失最常见（6例），其次是ARID1A（4例）、SMARCB1/INI1（2例）、SMARCA4（1例）和SMARCC1（1例）。这是第一项探索SWI/SNF在泌尿道未分化UC中表达的研究。我们的结果与最近的研究一致，这些研究报道SWI/SNF复合体参与了包括泌尿道在内的不同器官中多种上皮肿瘤的去分化过程，并与侵袭性临床病程相关。
