子宫去分化癌及未分化癌中SMARCA4 (BRG1)及SMARCB1(INI1)的表达及临床病理分析

Expression of SMARCA4(BRG1) and SMARCB1(INI1) in dedifferentiated and undifferentiated endometrial carcinomas and their correlations with clinicopathological features

目的探讨SMARCA4(BRG1)及SMARCB1(INI1)蛋白表达情况与子宫内膜去分化癌及未分化癌的临床病理特征及预后的相关性.方法收集2006年1月至2018年12月间复旦大学附属肿瘤医院病理科子宫去分化癌10例及未分化癌16例的手术及会诊病例共26例.收集临床病史,经2名病理医师复核病理诊断,复阅病理形态特征.采用免疫组织化学法检测BRG1和INI1蛋白,并分析表达状态与临床病理参数及预后的相关性.结果 BRG1和INI1蛋白表达缺失病例共计14例(14/26,53.8%),其中BRG1缺失12例,INI1缺失2例.14例蛋白表达缺失的病例中6例可见横纹肌样细胞,而阳性表达的12例中仅有1例具有该特征,但差异无统计学意义(P=0.060).年龄、浸润深度、淋巴结转移情况及国际妇产科联盟分期在表达与否的两组间差异均无统计学意义(P=0.437,P=0.672,P=0.242,P=0.348).BRG1和INI1蛋白缺失表达组的预后明显差于正常表达组(4.7个月比22.9个月,P=0.033).结论 BRG1和INI1蛋白表达缺失见于约1/2的子宫内膜未分化癌/去分化癌,蛋白缺失表达的病例更常见横纹肌样细胞,预后更差.推荐在含有未分化癌成分的内膜癌中加做BRG1和INI1,提高病理医师的鉴别诊断能力,帮助临床判断预后.

Objective To investigate the expression of SMARCA4 (BRG1) and SMARCB1 (INI-1) protein in endometrial dedifferentiated carcinoma (DDC) and undifferentiated carcinoma (UDC), and their correlation with clinicopathologic features. Methods Clinicopathological information was gathered for 26 cases of DDC and UDC and consulting hospitals from January, 2006 to December, 2018 in Fudan University Shanghai Cancer Center, including 10 cases of DDC and 16 cases of UDC. Morphologic features and diagnosis were reviewed by two pathologists. Immunohistochemistry for expression of BRG1 and INI1 protein was performed. The correlations with clinicopathologic features were analyzed. Results BRG1 and INI1 loss were present in 14 of 26 cases of DDC/UDC, including 12 BRG1-deficient cases and 2 INI1-deficient cases, respectively. Six cases demonstrated variable amounts of rhabdoid cells in 14 BRG1/INI1-deficient cases, and only 1 case showed rhabdoid cells in the 12 intact expression cases. However, there was no significantly statistical difference (P=0.060). Age, invasive depth, lymph node status and FIGO stage were not associated with the expression of the BRG1 and INI1 (P=0.437, P=0.672, P=0.242, P=0.348). Remarkably, the BGR1/INI1-deficient patients had worse survival than those with intact expression (4.7 vs. 22.9, P=0.033). Conclusion BRG1/INI1-deficient is observed in approximately half of DDC and UDC. Identification of these tumors is clinically relevant due to their more aggressive behavior and poor prognosis. Hence, BRG1 and INI1 immunohistochemical stains should be performed for DDC and UDC in order to help the pathologists to distinguish these tumors from other carcinomas, and to predict the clinical prognosis.