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

Yuka Kuroda, Tatsuyuki Chiyoda, Miho Kawaida, Kohei Nakamura, Eriko Aimono, Takuma Yoshimura, Mio Takahashi, Keiko Saotome, Tomoko Yoshihama, Naomi Iwasa, Kensuke Sakai, Wataru Yamagami, Hiroshi Nishihara, Daisuke Aoki

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)679-685
Number of pages7
JournalGynecologic Oncology
Volume162
Issue number3
DOIs
Publication statusPublished - 2021 Sep

Keywords

  • ARID1A
  • AT-rich interactive domain 1A
  • Immune therapy
  • Immunotherapy
  • Ovarian cancer
  • PD-L1

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology

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