The Overexpression of Programmed Death-Ligand 2 in Uterine Adenosarcoma: Correlation with High-Grade Morphology,
Alev Ok Atılgan1, Eda Yılmaz Akçay1, Özlem Özen1
1Department of Pathology, Faculty of Medicine, Baskent University, Bahcelievler, Ankara, Turkey.
Abstract:
Immunotherapy involving the programmed death-1 (PD-1)/the programmed death-ligand (PD-1/PD-L) blockade is an understudied tumor therapy approach in cases of adenosarcoma. PD-L1 and PD-L2, and tumor protein p53 (p53) were examined in 20 uterine adenosarcoma cases, and tumor-infiltrating lymphocytes and tumor-associated macrophages were counted in tumor tissue using immunohistochemistry. While CPS PD-L1 positivity with 1% and 10% cut-off values was observed in 40% and 10% of tumors, respectively, CPS PD-L2 positivity with 1%, 10% and 50% cut-off values was observed in 100%, 85% and 50% of the tumors, respectively. The CPS PD-L2 positivity with a 50% cut-off value was positively correlated with tumor grade and the presence of sarcomatous overgrowth and lymphovascular invasion (LVI) (p = 0.025, p = 0.025, and p = 0.025, respectively). Nine of 11 high-grade adenosarcomas and none of the low-grade adenosarcomas showed mutant type p53 expression (p = 0.000). However, PD-L1 expression and tumor-infiltrating immune cells did not correlate with clinicopathological parameters. The CPS PD-L2 positivity with a 50% cut-off value was also positively correlated with mutant type p53 expression (p = 0.024) and tumor-associated macrophages density (p = 0.024). The CPS PD-L2 positivity with a 50% cut-off value and mutant type p53 expression were associated with shorter disease-free survival and shorter overall survival. The high density of tumor-associated macrophages and low density of tumor-infiltrating lymphocytes were also associated with shorter disease-free survival and overall survival (p < 0.05).These results suggested that the CPS PD-L2 positivity with a 50% cut-off value, p53 mutation and tumor microenvironment played an essential role in the progression of uterine adenosarcomas.
Insights
Programmed death-ligand 2 (PD-L2) positivity and p53 mutations are linked to poorer outcomes in uterine adenosarcoma. These factors, along with the tumor microenvironment, are crucial in disease progression and warrant further investigation for immunotherapy strategies.
Area of Science:
- Gynecologic Oncology
- Cancer Immunology
- Tumor Microenvironment Research
Background:
- Immunotherapy targeting the programmed death-1 (PD-1)/programmed death-ligand (PD-1/PD-L) pathway is an emerging, yet understudied, therapeutic approach for adenosarcoma.
- Understanding the expression of PD-L1, PD-L2, and p53, along with immune cell infiltration, is critical for developing effective treatments.
Purpose of the Study:
- To investigate the expression of PD-L1, PD-L2, and p53 in uterine adenosarcoma.
- To correlate these markers with clinicopathological parameters and patient survival.
- To explore the role of tumor-infiltrating lymphocytes and tumor-associated macrophages in adenosarcoma progression.
Main Methods:
- Immunohistochemistry was used to examine PD-L1, PD-L2, and p53 expression in 20 uterine adenosarcoma tissue samples.
- Quantification of tumor-infiltrating lymphocytes and tumor-associated macrophages was performed.
- Statistical analysis was conducted to correlate marker expression with clinicopathological features and survival outcomes.
Main Results:
- PD-L2 positivity (at 50% cut-off) correlated with higher tumor grade, sarcomatous overgrowth, lymphovascular invasion (LVI), mutant p53 expression, and increased tumor-associated macrophages.
- High-grade adenosarcomas showed a higher prevalence of mutant p53 expression compared to low-grade tumors.
- PD-L2 positivity (50% cut-off) and mutant p53 expression were associated with shorter disease-free and overall survival.
- High density of tumor-associated macrophages and low density of tumor-infiltrating lymphocytes were linked to poorer survival outcomes.
Conclusions:
- PD-L2 positivity (50% cut-off), p53 mutation, and specific tumor microenvironment characteristics (high TAMs, low TILs) are significant prognostic factors in uterine adenosarcoma.
- These findings highlight the potential of PD-L2 and p53 as biomarkers and suggest the tumor microenvironment's critical role in disease progression.
- Further research into PD-1/PD-L blockade immunotherapy for adenosarcoma, considering these markers, is warranted.
