未分化/去分化子宫内膜癌(UDEC和DDEC)罕见,侵袭性子宫肿瘤,没有特定的分化线。这些病例的显著比例特征为SWI/SNF染色质重塑复合物成员的突变,包括ARID1A,SMARCA4和SMARCB1基因。为了更全面地研究这些实体,我们从我们的病理档案中确定了10个UDEC和10个DDEC,获得的临床病理结果和随访数据,并对ARID1A进行了免疫组织化学研究,BRG1(SMARCA4),和INI1(SMARCB1)蛋白。此外,我们成功地对23个样本进行了靶向下一代测序,包括7个UDEC,和7个未分化和9个良好/中等分化的DTEC成分。病例包括18例子宫切除术和2例刮宫/活检标本。患者年龄为47至77岁(中位数,59年),中位肿瘤大小为8.0厘米(范围,2.5-13.0厘米)。所有病例均表现为淋巴管浸润,大多数(13/20)为FIGOIII-IV期。通过免疫组织化学,在15例中观察到ARID1A丢失,4例BRG1缺失,所有病例均有完整的INI1表达。观察到DTEC中未分化成分因ARID1A损失而富集的趋势,虽然没有统计学意义。测序显示PTEN中常见的致病性突变,PIK3CA,ARID1A,CTNNB1和RNF43,一种复发性MAX致病突变,以及MYC和12p拷贝数增益。在DDEC中,与高/中分化成分相比,未分化成分具有更高的肿瘤突变负担;然而,突变景观在很大程度上重叠。总的来说,我们的研究为UDEC/DDEC的突变景观提供了深刻的见解,SWI/SNF染色质重塑复合物成员状态,以及它们与肿瘤特征的潜在关系。
Undifferentiated/dedifferentiated endometrial carcinomas (UDEC and DDEC) are rare, aggressive uterine neoplasms, with no specific line of differentiation. A significant proportion of these cases feature mutations of SWI/SNF chromatin remodeling complex members, including ARID1A, SMARCA4, and SMARCB1 genes. To study these entities more comprehensively, we identified 10 UDECs and 10 DDECs from our pathology archives, obtained clinicopathologic findings and follow-up data, and performed immunohistochemical studies for ARID1A,
BRG1 (SMARCA4), and INI1 (SMARCB1) proteins. In addition, we successfully conducted targeted next-generation sequencing for 23 samples, including 7 UDECs, and 7 undifferentiated and 9 well/moderately-differentiated components of DDECs. Cases consisted of 18 hysterectomies and 2 curettage/biopsy specimens. Patient age ranged from 47 to 77 years (median, 59 years), with a median tumor size of 8.0 cm (range, 2.5-13.0 cm). All cases demonstrated lymphovascular invasion and the majority (13/20) were FIGO stage III-IV. By immunohistochemistry, ARID1A loss was observed in 15 cases,
BRG1 loss in 4, and all cases had intact INI1 expression. A trend for enrichment of the undifferentiated component of DDECs for ARID1A loss was seen, although not statistically significant. Sequencing revealed frequent pathogenic mutations in PTEN, PIK3CA, ARID1A, CTNNB1, and RNF43, a recurrent MAX pathogenic mutation, and MYC and 12p copy number gains. In DDECs, the undifferentiated component featured a higher tumor mutational burden compared to the well/moderately-differentiated component; however, the mutational landscape largely overlapped. Overall, our study provides deep insights into the mutational landscape of UDEC/DDEC, SWI/SNF chromatin remodeling complex member status, and their potential relationships with tumor features.