Molecular subtypes and quantitative analysis of PD-L1 and tumor-associated immune cells in uterine carcinosarcoma.

Objective: In the present study, molecular subtypes were determined, programmed death-ligand 1 (PD-L1) and tumor-associated immune cells (TAICs) were quantitatively detected, and their effect on prognosis in uterine carcinosarcoma (UCS) was analyzed.

Methods: The study included 65 UCS cases. Direct sequencing of POLE exonuclease domain and immunohistochemistry of mismatch repair (MMR) deficiency proteins and p53 were used to stratify molecular subtypes. QuPath was used for quantitative immunohistochemical detection of PD-L1 and TAICs. The chi square test was used to determine the association between molecular subtypes and expression of PD-L1 and TAICs. The Kaplan-Meier method and Cox proportional hazards regression were used for plotting and survival analysis.

Results: In 65 UCS cases, 1 case (1.5%) was POLE ultramutated (POLEmut) subtype, 11 cases (16.9%) were deficient MMR (dMMR) subtype, 32 cases (49.3%) were p53 mutant (p53mut) subtype, and 21 cases (32.3%) were nonspecific molecular profile (NSMP) subtype. The positive density of PD-L1 in tumor (p=0.022), CD8 in stroma (p=0.036), and CD163 in stroma (p=0.025) were significantly associated with molecular subtypes. The patients with POLEmut and dMMR subtypes had a relatively better prognosis trend than patients with NSMP and p53mut subtypes. The patients with high positive density of PD-L1 in tumor had significantly better prognosis; however, high positive density of CD163 in stroma showed significantly worse prognosis.

Conclusion: UCS could be classified into four molecular subtypes associated with prognosis. PD-L1 and M2 macrophages could effectively predict the prognosis of patients with UCS.