ARID1A 突变/ARID1A 缺失与透明细胞卵巢癌中的高免疫原性特征相关。

ARID1A mutation/ARID1A loss is associated with a high immunogenic profile in clear cell ovarian cancer.

机构信息

Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.

出版信息

Gynecol Oncol. 2021 Sep;162(3):679-685. doi: 10.1016/j.ygyno.2021.07.005. Epub 2021 Jul 14.

DOI:10.1016/j.ygyno.2021.07.005

PMID:34272091

Abstract

OBJECTIVES

ARID1A mutation is frequently found in clear cell ovarian cancer (CCC) and endometrioid ovarian cancer (EC). Anti-PD-1 monotherapy has been found to have limited efficacy in epithelial ovarian cancer; however, anti-PD-1 therapy showed significant clinical benefit in some CCC. We sought to define the relationship of ARID1A mutation/ARID1A expression to the immunogenic profile of different histologic subtypes of ovarian cancer.

METHODS

We performed next-generation sequencing of 160 cancer-related genes. Also, we analyzed the immunohistochemical status of ARID1A, PD-L1, and CD8 with survival in different histologic subtypes of ovarian cancer in a total of 103 cases.

RESULTS

ARID1A mutation was found in 0% of the high-grade serous ovarian cancer (HGSC) (n = 36), 41.5% of the CCC (n = 41), 45.0% of the EC (n = 20), and 33.3% of the mucinous ovarian cancer (MC) (n = 6) cases. ARID1A loss was found in 19.4% of the HGSC, 75.6% of the CCC, 60.0% of the EC and 0% of the MC cases. ARID1A mutation was found to be associated with high PD-L1 (p < 0.001) or CD8 levels (p < 0.001) in CCC but not in other histologic subtypes. Meanwhile, ARID1A loss was associated with high PD-L1 or CD8 levels in CCC (p < 0.001) and HGSC (p < 0.001) but not in EC and MC. In addition, ARID1A mutation was associated with high tumor mutation burden in CCC (p = 0.006).

CONCLUSIONS

ARID1A mutation/ARID1A expression is associated with immune microenvironmental factors in CCC but not in EC. ARID1A status can be a biomarker for selecting candidates for immune checkpoint blockade in CCC.

摘要

目的

ARID1A 突变在透明细胞卵巢癌（CCC）和子宫内膜样卵巢癌（EC）中经常发现。抗 PD-1 单药治疗已被发现对上皮性卵巢癌疗效有限；然而，抗 PD-1 治疗在一些 CCC 中显示出显著的临床获益。我们试图确定 ARID1A 突变/ARID1A 表达与不同组织学类型卵巢癌免疫原性特征的关系。

方法

我们对 160 个癌症相关基因进行了下一代测序。此外，我们在总共 103 例不同组织学类型的卵巢癌中分析了 ARID1A、PD-L1 和 CD8 的免疫组化状态与生存的关系。

结果

高级别浆液性卵巢癌（HGSC）（n=36）中未发现 ARID1A 突变，CCC（n=41）中 41.5%，EC（n=20）中 45.0%，黏液性卵巢癌（MC）（n=6）中 33.3%。HGSC 中发现 19.4%的 ARID1A 缺失，CCC 中发现 75.6%，EC 中发现 60.0%，MC 中发现 0%。在 CCC 中，ARID1A 突变与高 PD-L1（p<0.001）或 CD8 水平（p<0.001）相关，但在其他组织学类型中不相关。同时，在 CCC（p<0.001）和 HGSC（p<0.001）中，ARID1A 缺失与高 PD-L1 或 CD8 水平相关，但在 EC 和 MC 中不相关。此外，在 CCC 中，ARID1A 突变与高肿瘤突变负担相关（p=0.006）。