SWI/SNF Chromatin-remodeling Complex Status in SMARCB1/INI1-preserved Epithelioid Sarcoma
SWI/SNF Chromatin-remodeling Complex Status in SMARCB1/INI1-preserved Epithelioid Sarcoma
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DOI：
10.1097/pas.0000000000001011
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发表时间：
2018-03-01
影响因子：
5.6
通讯作者：
Oda, Yoshinao
中科院分区：
文献类型：
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作者：
Kohashi, Kenichi;Yamamoto, Hidetaka;Oda, Yoshinao
SWI/SNF染色质重塑复合物由进化上保守的核心亚基如SMARCB 1/INI 1（INI 1）、SMARCA 4/BRG 1（BRG 1）、SMARCC 1/BAF 155（BAF 155）和SMARCC 2/BAF 170（BAF 170）组成，可以被视为参与肿瘤抑制的基因表达的表观遗传调节因子的原型。上皮样肉瘤是一种分化程度不确定的肿瘤，其INI 1几乎完全缺失。然而，一些上皮样肉瘤的病例保留了INI 1，这些病例的临床病理特征尚不确定。到目前为止，还没有调查集中在SWI/SNF染色质重塑复合物在INI 1保存上皮样肉瘤的情况下。首先，在60例福尔马林固定石蜡包埋的上皮样肉瘤标本（近端型，29例;常规型，31例）中进行INI 1免疫表达状态的调查。在现有的INI 1保留的上皮样肉瘤病例中，我们分析了BRG 1、BAF 155和BAF 170蛋白的表达。在29例近端型和31例常规型上皮样肉瘤中分别有6例（21%）和2例（6%）观察到INI 1保留。6例近端型上皮样肉瘤的INI 1蛋白表达可用于进一步的免疫组化研究。1例近端型显示BAF 170缺失，2例近端型显示BRG 1缺失，其他核心亚基蛋白保留。1例近端型病例显示BRG 1的镶嵌模式和BAF 155的缺失。然而，在剩余的2个近端型病例中，所有核心亚基蛋白被保留。总之，这些结果表明，SWI/SNF染色质重塑复合物蛋白表达的丧失在肿瘤发生中具有重要作用。其余2例INI 1保留的上皮样肉瘤病例可能有其他异常，导致SWI/SNF染色质重塑功能障碍。
The SWI/SNF chromatin-remodeling complex, which is composed of evolutionarily conserved core subunits such as SMARCB1/INI1 (INI1), SMARCA4/BRG1 (BRG1), SMARCC1/BAF155 (BAF155), and SMARCC2/BAF170 (BAF170), can be viewed as the prototype of an epigenetic regulator of gene expression that is involved in tumor suppression. Epithelioid sarcoma, which classified as a tumor of uncertain differentiation, shows an almost complete loss of INI1. However, some cases of epithelioid sarcoma have preserved INI1, and the clinicopathologic features of these cases are uncertain. To date, there has been no investigation focused on the SWI/SNF chromatin-remodeling complex in INI1-preserved epithelioid sarcoma cases. First, an investigation of INI1 immunoexpression statuses in 60 formalin-fixed paraffin-embedded epithelioid sarcoma specimens (proximal type, 29 cases; conventional type, 31 cases) was performed. In the available INI1-preserved epithelioid sarcoma cases, we analyzed the BRG1, BAF155, and BAF170 protein expressions. INI1 preservation was observed in 6 of 29 (21%) proximal-type and 2 of 31 (6%) conventional-type epithelioid sarcoma cases. Six cases of INI1-preserved epithelioid sarcomas of proximal type were available for further immunohistochemical study. One proximal type showed loss of BAF170, and 2 proximal-type cases revealed loss of BRG1 with preservation of the other remaining core subunit proteins. One proximal-type case showed a mosaic pattern of BRG1 and loss of BAF155. However, in the remaining 2 proximal-type cases, all core subunit proteins were preserved. Overall, these results suggest that loss of expression of SWI/SNF chromatin-remodeling complex proteins has an important role in tumorigenesis. The remaining 2 INI1-preserved epithelioid sarcoma cases may have had other abnormalities causing dysfunction of SWI/SNF chromatin remodeling.