Impact of TSC2 loss on progression-free survival in uterine carcinosarcoma: A retrospective analysis

Objective: Uterine carcinosarcoma (UCS) is a rare and aggressive gynecological cancer with high recurrence rates and is associated with a poor prognosis. It is also characterized by a high frequency of copy number alterations (CNAs). This study aimed to determine which gene CNA contributes to progression-free survival (PFS) in patients with UCS to identify potential prognostic biomarkers and therapeutic targets. Methods: DNA was extracted from formalin-fixed paraffin-embedded tissues of surgical specimens from 24 patients with UCS who were treated at Fujita Health University. Using the PleSSision-Rapid test, the mutation information of 145 cancer genes was analyzed. Oncoplot analysis was used to visualize gene mutation profiles. χ² test, Kaplan– Meier analysis, and log-rank test were used for statistical analyses. Results: The most frequently observed gene mutation was TP53 in the 24 UCS cases studied, while genes associated with the PI3K/AKT/mTOR signaling pathway, including PIK3CA, PTEN, PIK3R1, and PIK3R2 were commonly detected. In the χ² test analysis, TP53 loss (p=0.029), PIK3CA amplification (p=0.034), and TSC2 loss (p=0.034) were significantly associated with recurrence. Kaplan–Meier survival analysis demonstrated a significant association between PIK3CA amplification and TSC2 loss with PFS, as determined by the log-rank test (p<0.05). Conclusion: In patients with UCS, TSC2 loss is linked to poorer PFS, highlighting its utility as a prognostic marker. The association between TSC2 loss and increased recurrence risk highlights the potential therapeutic advantage of targeting the mTOR pathway in TSC2-deficient tumors.