Abstract
Introduction/Objective
Upregulation of programmed death-ligand 1 (PD-L1), an immunoregulatory protein is associated with adverse outcome in several malignancies. Very few studies have evaluated PD-L1 expression in anal squamous cell carcinoma. This study aims to correlate PD-L1 expression with clinicopathologic factors and clinical outcomes.
Methods
After IRB approval, formalin-fixed, paraffin embedded sections of 58 cases of anal invasive squamous cell carcinoma from 2010–2018 were immunostained for PD-L1 (Dako 22C3 monoclonal antibody). Of these, 51 cases could be evaluated for PD-L1 expression. Greater than 1% of tumor cells with partial or complete membrane staining was interpreted as PD-L1 positive (PD-L1 +). PD-L1 expression was correlated with age, sex, stage, HIV status, HIV viral load, CD4 count, disease progression, and cancer specific survival. Kaplan-Meier curves for overall survival (OS) were plotted and compared using the log rank test. Cox regression analysis was performed to identify significant prognostic factors (Two-tailed p< 0.05 was considered statistically significant).
Results
Of the 51 cases evaluated, PD-L1 was positive in 18/51 (35%) and negative in 33/51 (65%) cases. The median cancer specific survival (MCSS) was lower in PD-L1 positive cases (22 months) compared with PD-L1 negative cases (48 months), p=0.008. The number of cancer specific deaths was higher in the PD-L1 + group (50% vs. 30%), but not statistically significant (p= 0.23). Other factors that were not significantly different between the two groups were age, sex, stage, HIV status, HIV viral load, and number of patients with cancer progression. Patients with positive PD-L1 had worse OS (5yr OS: 41% for PD-L1 positive vs 64% for PD-L1 negative; p=0.02). On multivariate analysis, PD-L1 positive status remained statistically significant for worse OS, HR = 6.5 (95% CI 1.2–33.9), p=0.027.
Conclusion
The median cancer specific survival and 5-yr OS is significantly lower in the PD-L1 positive group. PD-L1 positive status is associated with a worse prognosis independent of stage, HIV status, HIV viral load, and CD4 count. The study highlights the potential of PD-L1 targeted therapy in better management of anal squamous cell carcinoma.
Association of HIV Status With Local Immune Response to Anal Squamous Cell Carcinoma