ARID1A deficiency associated with MMR deficiency and a high abundance of tumor-infiltrating lymphocytes predicts a good prognosis of endometrial carcinoma

Dantong Sun; Han Zhao; Hai Zhou; Junyan Tao; Tianjun Li; Jingjuan Zhu; Helei Hou

doi:10.1016/j.tranon.2023.101685

ARID1A deficiency associated with MMR deficiency and a high abundance of tumor-infiltrating lymphocytes predicts a good prognosis of endometrial carcinoma

Transl Oncol. 2023 Jul:33:101685. doi: 10.1016/j.tranon.2023.101685. Epub 2023 May 1.

Authors

Dantong Sun¹, Han Zhao², Hai Zhou³, Junyan Tao³, Tianjun Li³, Jingjuan Zhu³, Helei Hou⁴

Affiliations

¹ National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
² Department of Pathology, The Affiliated Hospital of Qingdao University, 266000, Qingdao, China.
³ Precision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China.
⁴ Precision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China. Electronic address: houhelei@qdu.edu.cn.

Abstract

Background: ARID1A alterations have been detected in 40% of endometrial carcinomas (ECs) and are associated with loss of its expression. The role of ARID1A in tumorigenesis and development is complex, and the prognostic role in EC remains controversial. Hence, it is of great significance to confirm the role of ARID1A in EC.

Methods: A total of 549 EC patients (cohort A) from TCGA were evaluated to explore the prognostic role of ARID1A. NGS was performed for 13 EC patients (cohort B), and expression of ARID1A, CD3, CD8 and mismatch repair (MMR) proteins in 52 patients (cohort C) from our center was determined by immunohistochemistry (IHC). The Kaplan-Meier method was used to perform survival analyses.

Results: ARID1A alterations were detected in 32% of EC patients and correlated with good disease-free survival (DFS, P = 0.004) and overall survival (OS, P = 0.0353). ARID1A alterations were found to co-occur with MMR-related gene mutations and correlated with higher PD-L1 expression. Patients concomitantly harboring ARID1A alterations and MMR-related gene mutations had the best prognosis (DFS: P = 0.0488; OS: P = 0.0024). A cohort from our center showed that ARID1A deficiency was an independent prognostic factor and predicted longer recurrence-free survival (P = 0.0476). ARID1A loss was associated with a tendency toward MSI-H (P = 0.0060). ARID1A alterations and expression loss were associated with a higher abundance of CD3+ (P = 0.0406) and CD8+ (P = 0.0387) T cells.

Conclusion: ARID1A alterations and expression loss are tightly associated with MMR deficiency and a high abundance of tumor-infiltrating lymphocytes, which might contribute to the good prognosis of EC.

Keywords: ARID1A; Endometrial carcinoma; Mismatch repair; Prognosis; Tumor microenvironment.