AP-HP, Département de Pathologie, Hôpital H. Mondor - A. Chenevier, Créteil, France.
Histopathology. 2012 Sep;61(3):428-35. doi: 10.1111/j.1365-2559.2012.04228.x. Epub 2012 Jun 11.
Renal medullary carcinoma (RMC), a rare and highly aggressive tumour which occurs in patients with sickle-cell disease, shares many clinicopathological features with collecting duct carcinoma (CDC). The molecular mechanisms underlying RMC and CDC are mainly unknown, and there is ongoing debate about their status as distinct entities. Loss of expression of SMARCB1/INI1, a chromatin remodelling regulator and repressor of cyclin D1 transcription, has been reported recently in RMC. The aim of our study was to investigate if such loss of expression is specific for RMC. SMARCB1/INI1 genetic alterations and cyclin D1 expression were also studied.
Using immunochemistry, neoplastic cells showed complete loss of SMARCB1/INI1 expression in all six cases of RMC but in only one of 22 cases of CDC. In two RMC cases investigated, comparative genomic hybridization demonstrated complete loss of one SMARCB1/INI1 allele, with no other genomic imbalances, and no mutations were found on the remaining allele. Cyclin D1 was expressed in all RMCs, suggesting that SMARCB1/INI1 inactivation may result in increased cyclin D1 transcription.
The specific SMARCB1/INI1 inactivation observed in RMCs suggests that RMC and CDC are different entities.
肾髓质癌（RMC）是一种罕见且高度侵袭性的肿瘤，发生于镰状细胞病患者，其与集合管癌（CDC）具有许多临床病理特征。RMC 和 CDC 的分子机制主要未知，关于它们是否为不同实体的争论仍在继续。最近有报道称，染色质重塑调节剂和细胞周期蛋白 D1 转录抑制剂 SMARCB1/INI1 的表达缺失存在于 RMC 中。本研究旨在探讨这种表达缺失是否是 RMC 所特有的。还研究了 SMARCB1/INI1 基因改变和 cyclin D1 的表达。
使用免疫化学方法，在所有 6 例 RMC 中，肿瘤细胞均完全缺失 SMARCB1/INI1 表达，但在 22 例 CDC 中仅 1 例缺失。在 2 例 RMC 病例中，比较基因组杂交显示一个 SMARCB1/INI1 等位基因完全缺失，没有其他基因组失衡，另一个等位基因未发现突变。所有 RMC 均表达 cyclin D1，表明 SMARCB1/INI1 失活可能导致 cyclin D1 转录增加。
在 RMC 中观察到的特异性 SMARCB1/INI1 失活表明 RMC 和 CDC 是不同的实体。
