PD-L1 expression and association with malignant behavior in pheochromocytomas/paragangliomas

The immunosuppressive effect of the programmed death (PD)-1/PD-L1 pathway plays an important role in the treatment of a variety of tumors, such as lung and breast cancer, but there is little literature about PD-1/PD-L1 in pheochromocytomas/paragangliomas (PCCs/PGLs). We explored the relationship of PD-L1 and malignant behavior in 77 cases of PCC/PGL using immunohistochemistry (IHC) to assess protein expression and RNAscope to detect mRNA expression in 20 cases. The IHC data showed that 59.74% of the PCCs/PGLs expressed PD-L1, and the extent of expression was highly correlated with Ki-67 (P = .019) and hypertension (P = .013) but not with age, sex, tumor size, capsular invasion, tumor necrosis, relapse/distant metastasis, secretion of noradrenaline/adrenaline/dopamine, or diabetes mellitus. In addition, we found an excellent correlation of PD-L1 mRNA and protein expression with a κ coefficient of 0.828, and further stratification of the IHC and RNAscope findings showed high consistency (Pearson coefficient 0.753). The correlation of PD-L1 and Ki-67 indicated that PD-L1 could be considered a malignant proliferation biomarker for PCCs/PGLs, which would be a putative biomarker for anti-PD-L1 therapies.