[Characteristics of uterine leiomyosarcoma: a clinicopathological and molecular genetic analysis of twenty-four cases].

Objective: To investigate the clinicopathological and molecular genetic characteristics of uterine leiomyosarcoma. Methods: A retrospective study was performed on twenty-four patients diagnosed with uterine leiomyosarcoma, at Peking University, Third Hospital, from January 2023 to July 2024. The study aimed to analyze the clinicopathological characteristics of uterine leiomyosarcoma using immunohistochemistry and next generation sequence to detect the molecular genetic alterations. Results: Among the twenty-four cases, patient's age ranged from 29 to 74 years, with a median age of 45.5 (37.5, 49.3) years. Tumor size ranged from 6 to 20 cm, with an average size of 11 cm. Before surgery, sixteen patients had received hormone therapy, traditional Chinese medicine, health supplements, and/or oxytocin during surgery. Among these sixteen cases, eight cases showed morphological changes of the tumor cells, with the nature of necrosis being difficult to characterize, posing diagnostic challenges. Immunohistochemical analysis revealed positive expression of smooth muscle markers in all 24 cases. A mutant p53 expression pattern was observed in 14 cases, while loss of Rb expression was noted in 17 cases. Loss of ATRX and PTEN expression was detected in 13 and 11 cases, respectively.All twenty-four cases demonstrated microsatellite stability. Twenty-three cases showed a low tumor mutational burden (TMB), while one case showed high TMB. All cases showed variations of copy number and gene mutations involving multiple genes. The most common molecular genetic aberrations were loss of copy number or mutation in TP53 and RB1. Simultaneous genetic aberrations in both TP53 and RB1 were identified in fifteen cases. Furthermore, eleven cases showed copy number loss of BRCA2 and one case showed a missense mutation of BRCA2. Twenty-one cases revealed frequent copy number variations in homologous recombination repair-related genes, including FANCA, FANCM, RAD51B, BARD1, FANCE, ATM, CHEK2 etc. Thirteen cases showed loss of ATRX protein expression. Conclusions: Uterine leiomyosarcoma is characterized by multiple copy number variations and gene mutations, most frequently involving TP53 and RB1. Additional common molecular features include copy number variations of homologous recombination repair-related genes, ATRX protein expression loss, low tumor mutational burden, and microsatellite stability. Secondary morphological changes in uterine leiomyosarcomas associated with hormone therapy pose significant diagnostic challenges. Next generation sequencing can provide valuable evidence for the diagnosis of morphologically challenging cases of leiomyosarcoma in clinical practice.