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Abstract
Objective As 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 of ARID1A in endometrial cancers of NSMP subtype.
Methods Prospectively 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. ARID1A mutational status, as defined by full-length gene sequencing, was matched with risk of recurrence, progression-free and disease-specific survival within the NSMP cohort.
Results A total of 127 patients with endometrial cancer were included. Among 72 patients with tumors of NSMP subtype (56.7%), ARID1A mutations were identified in 24 cases (33.3%). ARID1A mutations 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).
Conclusion ARID1A appears 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, ARID1A assessment could help to further sub-classify selected endometrial cancers and improve personalized treatment strategies.
- Endometrium
Data availability statement
Data are available upon reasonable request. Raw data were generated at the Medical University of Vienna. Derived data supporting the findings of this study are available from the corresponding author on request.
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Data availability statement
Data are available upon reasonable request. Raw data were generated at the Medical University of Vienna. Derived data supporting the findings of this study are available from the corresponding author on request.
Footnotes
Contributors Conceptualization: AO, TB and CG. Data curation: AO, TD and GH. Formal analysis: AO, TB, SP and LM. Investigation: TD, GH. Methodology: AO and TB. Project administration: CG. Resources: SP, CG, GH and LM. Software: AO and TB. Supervision: CG. Validation: CG, SP and GH. Visualization: AO and TB. Writing—original draft preparation: AO and TB. Writing—review and editing: GH and CG. Guarantor for overall content: AO.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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