Renal medullary carcinoma: rhabdoid features and the absence of INI1 expression as markers of aggressive behavior
Renal medullary carcinoma: rhabdoid features and the absence of INI1 expression as markers of aggressive behavior
复制标题
DOI：
10.1038/modpathol.2008.44
复制
发表时间：
2008-06-01
期刊：
影响因子：
7.5
通讯作者：
Taxy, Jerome B.
中科院分区：
文献类型：
--
作者：
Cheng, Jason X.;Tretiakova, Maria;Taxy, Jerome B.
肾髓质癌是一种罕见的、公认的高度侵袭性肿瘤，具有不同的组织病理学，发生在具有镰状细胞特征或疾病的年轻患者中。横纹肌样分子偶尔见于高级别肾肿瘤，包括肾髓样癌，可能代表侵袭性行为的病理标志。INI1(hSNF5/SMARCB1/BAF47)是ATP依赖的染色质修饰复合体中的一个高度保守的因子。在小鼠身上失去这一因子会导致侵袭性横纹肌样肿瘤或淋巴瘤。在人类中，INI1的表达缺失在儿童肾横纹肌样瘤、中枢神经系统不典型畸胎样/横纹肌样瘤和上皮样肉瘤中被报道，上皮样肉瘤可能是一种原发的软组织横纹肌样瘤。这项研究比较了5例肾髓样癌和10例高级别肾细胞癌(5例具有横纹肌样征)、2例尿路上皮癌和2例儿童肾横纹肌样瘤。与儿童肾横纹肌样肿瘤相似，所有5例肾髓样癌均表现为INI1表达完全缺失，与组织病理学无关。相反，所有肾细胞癌或尿路上皮癌，包括那些具有组织学横纹肌样特征的肿瘤，都表达INI1。临床上，5例肾髓样癌患者和2例横纹肌样瘤患者在诊断时均有肾外转移。本研究表明肾髓样癌和肾横纹肌样瘤具有共同的分子/基因改变，这与它们的侵袭性生物学行为密切相关。然而，INI1表达缺失并不一定预示横纹肌样组织病理学，但仍与肾髓样癌的侵袭性行为有关。
Renal medullary carcinoma is a rare, well-recognized highly aggressive tumor of varied histopathology, which occurs in young patients with sickle cell trait or disease. Rhabdoid elements, occasionally seen in high-grade renal tumors including renal medullary carcinoma, possibly represent a pathologic marker of aggressive behavior. INI1 (hSNF5/SMARCB1/BAF47) is a highly conserved factor in the ATP-dependent chromatin-modifying complex. Loss of this factor in mice results in aggressive rhabdoid tumors or lymphomas. In humans, the loss of INI1 expression has been reported in pediatric renal rhabdoid tumors, central nervous system atypical teratoid/rhabdoid tumors and epithelioid sarcomas, a possible primary soft tissue rhabdoid tumor. This study compares five renal medullary carcinomas with 10 high-grade renal cell carcinomas (five with rhabdoid features), two urothelial carcinomas and two pediatric renal rhabdoid tumors. All five renal medullary carcinomas, irrespective of histopathology, showed complete loss of INI1 expression similar to that seen in pediatric renal rhabdoid tumors. In contrast, all renal cell carcinomas or urothelial carcinomas, including those with histological rhabdoid features, expressed INI1. Clinically, all five of the patients with renal medullary carcinoma and the two patients with rhabdoid tumors presented with extra-renal metastases at the time of diagnosis. This study demonstrates that renal medullary carcinoma and renal rhabdoid tumor share a common molecular/genetic alteration, which is closely linked to their aggressive biological behavior. However, the absence of INI1 expression is not necessarily predictive of rhabdoid histopathology but remains associated with aggressive behavior in renal medullary carcinoma.