Abstract
ObjectiveAs more than 50% of newly diagnosed endometrial cancers remain classified as ‘no specific molecular subtype’ (NSMP) due to a lack of established biomarkers to further improve molecular subtyping, this study aims to evaluate the prognostic value ofARID1Ain endometrial cancers of NSMP subtype.MethodsProspectively collected molecular profiling data of all consecutive patients with endometrial cancer who underwent primary surgery at our department between August 2017 and June 2022 and for whom both molecular profiling and clinical follow-up data were available were retrospectively evaluated. Tumor specimens were evaluated by combined mismatch repair protein immunohistochemistry and targeted next-generation hotspot sequencing.ARID1Amutational status, as defined by full-length gene sequencing, was matched with risk of recurrence, progression-free and disease-specific survival within the NSMP cohort.ResultsA total of 127 patients with endometrial cancer were included. Among 72 patients with tumors of NSMP subtype (56.7%),ARID1Amutations were identified in 24 cases (33.3%).ARID1Amutations were significantly associated with a higher risk of recurrence (37.5% vs 12.5%, OR 4.20, 95% CI 1.28 to 13.80, p=0.018) and impaired progression-free survival (HR 3.96, 95% CI 1.41 to 11.15, p=0.009), but not with disease-specific survival. The results for both risk of recurrence (OR 3.70, 95% CI 1.04 to 13.13, p=0.043) and progression-free survival (HR 3.19, 95% CI 1.10 to 9.25, p=0.033) were confirmed in multivariable analysis compared with advanced tumor stage International Federation of Gynecology and Obstetrics (2009) (FIGO ≥III) and impaired Eastern Clinical Oncology Group performance status (ECOG ≥1).ConclusionARID1Aappears to identify patients with endometrial cancer of NSMP subtypes with a higher risk of recurrence and could be used as a future prognostic biomarker. After clinical validation,ARID1Aassessment could help to further sub-classify selected endometrial cancers and improve personalized treatment strategies.