Insights into disease progression in endometrial cancers: The role of cell proliferation pathway mutations following adjuvant therapy.

e17633 Background: Endometrial cancer, a common malignancy of the uterine lining, is typically treated with through hysterectomy. Mutations in cell proliferation, tumor suppression, and mismatch repair (MMR) pathways play a crucial role in the development and progression of these cancers. With surgery and adjuvant therapy being the most common treatment practice, mutational profiling may be significant to predict treatment outcomes and recurrence risk. This study investigates the potential of genomic alterations in predicting disease progression, recurrence and therapy response in endometrial cancers in accordance with clinical treatment and follow-up. Methods: We investigated the mutational profiles of 40 endometrial cancer patients in adjunct with clinical follow-up data. A total of twenty patients had clinical follow-up data wherein 19 patients had previously undergone surgery and 16 had underwent adjuvant therapy. Next Generation Sequencing (NGS) test was performed using OncoIndx Assay (Aarthi et al., 2024). Results: Molecular analysis of 40 patient with regular follow up of 70% (from 3 months to 1-year post-surgery) indicated alterations in cell proliferation pathway, 25% carried tumor suppressor pathway alterations, while 20% showed alterations in MMR pathway genes. A total of 60% of patients underwent brachytherapy (adjuvant therapy), of which 33.3% exhibited presence of PTEN mutations and 25% showed PIK3CA mutations with no disease progression. Only two patients progressed towards recurrence in supraclavicular node and brain and with molecular profiles positive for TP53 (p.C141R, p.K132T), PIK3CA (p.E545A, p.H1047Y), PTEN (p.K267Rfs*9), BRCA1 (p.K339Rfs*2), MSH2 (p.L280Ffs*4, p.V367*), FGFR1 (p.N546D), and CIC (p.P1418Hfs*14) genes. Presence of compound TP53 and MMR gene mutations could be instrumental in the recurrence pattern despite adjuvant brachytherapy. In addition, 20% (n=4/20) of patients have also been detected with high MSI but none treated with immunotherapy. Conclusions: With a background of genomic profiling, with surgery and/or adjuvant therapy, diverse disease progressive behavioral pathways were identified. Genes including PTEN and PIK3CA with alterations were predominant among patients who underwent brachytherapy which could be a useful indicator of therapeutic response. With proliferative mutations predominantly identified in post-surgical patients, a longitudinal mutational monitoring could offer valuable insights to disease progression and treatment outcomes.