The features and prognostic value of ARID1A mutation and protein expression in endometrial cancer of no specific molecular profile (NSMP) subtype: a retrospective study in a large Chinese cohort.

Endometrial cancer (EC) of no specific molecular profile (NSMP) subtype constitutes the majority of EC and shows significant heterogeneity. This study aims to explore the role of ARID1A mutation and protein expression in NSMP EC patients in a large Chinese cohort. A retrospective analysis was conducted on patients with NSMP EC who underwent primary surgery and next-generation sequencing (NGS). Clinicopathologic features, ARID1A mutation, protein expression and progression-free survival (PFS) were analysed in our study. A total of 547 patients were enrolled in the study, and 151 patients with NSMP were included in the final analyses. ARID1A mutations were identified in 49.0% (74/151) patients, in which 85.1% (63/74) of them were loss-of-function mutations and 27.0% (20/74) with multiple mutations. Compared to patients with ARID1A wild-type, those with ARID1A mutations were older (p = 0.032) and had higher staging (p = 0.022), and ARID1A mutation was associated with poorer PFS (p = 0.019). Among 90 patients with immunohistochemistry (IHC), the absence of ARID1A protein expression was significantly associated with ARID1A mutation (p < 0.001), especially with ARID1A multiple mutations (p = 0.042). The aberrant PI3K pathway was more likely to occur in patients with ARID1A mutations (p = 0.006). ER/PR negative expression, PIK3CA hotspot mutations, with ARID1A mutations were correlated with poor PFS (p < 0.001; p = 0.013). ARID1A mutation was associated with worse PFS for patients with NSMP. ARID1A protein expression was significantly associated with ARID1A mutation. ARID1A mutation, with ER/PR expression and PIK3CA mutation status, could serve as the potential biomarkers to subclassify NSMP subtype and provide more precise therapeutic target.