Significance of TCGA molecular classification in fertility-sparing treatment of endometrial cancer and atypical hyperplasia.

Objective: To investigate The Cancer Genome Atlas (TCGA) molecular classification of endometrial cancer (EC) and endometrial atypical hyperplasia (AH) treated with fertility-sparing therapy. Methods: A total of 46 EC and AH patients who received fertility-sparing therapy and TCGA molecular classification tested by next generation sequencing, in Peking University People’s Hospital from June 2020 to December 2021, were retrospectively collected. We analyzed the relationship between molecular classification and clinicopathological factors and treatment outcomes. Results: Of the 46 patients, including 40 EC and 6 AH patients, 70.5% (32 patients) had complete remission (CR) after treatment, with median CR time of 8 months. The cases were distributed as no specific molecular profile (NSMP; n=34, 73.9%) subtype mainly, microsatellite instability-high (MSI-H; n=7, 15.2%), POLE ultra-mutated (n=3, 6.5%), and copy number high (CNH; n=2, 4.3%). Patients with MSI-H subtype had lower body mass index (24.0±5.5 kg/m² ), more family history of tumor (6/7), more with loss of mismatch repair protein expression by immunohistochemical (7/7), and higher Ki67 expression level (3/3). Patients in MSI-H subgroup had the lowest CR rate at 6 months (0/6, p=0.019), and survival analysis showed that such patients were less likely to achieve CR than those with NSMP subtype (p=0.022). Subgroup analysis of patients with NSMP showed that, age ≥30 years and diabetes mellitus related with longer treatment time to CR (p=0.01 and p=0.059, respectively). In addition, CR was obtained in 2 (2/3) POLE ultra-mutated cases and 1 (2/2) CNH case, respectively. Conclusion: TCGA molecular classification relates with the treatment response in patients with EC and AH treated with fertilitysparing therapy. Patients with MSI-H subtype have poor treatment efficacy. [ABSTRACT FROM AUTHOR]