Expression of PD-L1/PD-L2 is associated with high proliferation index of Ki-67 but not with TP53 overexpression in chondrosarcoma

Abstract

Purpose: Chondrosarcoma is a malignancy affecting cartilage and is chemo- and radio-resistant. Novel immune checkpoint inhibitors may play a role in treatment; however, expression of programmed cell death ligand 1/2 (PD-L1/PD-L2) in chondrosarcoma is unreported. Methods: Chondrosarcoma sections were collected and stained immunohistochemically for PD-L1, PD-L2, Ki-67, and TP53. Clinicopathological parameters were collected and analyzed statistically for associations and correlations. PD-L1/PD-L2 positivity was designated using 1% and 5% cutoffs, respectively. Results: A total of 59 chondrosarcoma samples excised between 1997 and 2017 were collected. There were 40 samples assessed as PD-L1-positive and 25 samples as PD-L2-positive. In univariate analysis, PD-L1 positivity was significantly associated with younger age ( P = .001), larger tumor ( P = .025), advanced tumor grade ( P < .001), and recurrence ( P < .001). PD-L1 positivity was not associated with gender, location, serum level of lactate dehydrogenase, or serum level of alkaline phosphatase. PD-L2 positivity was solely significantly associated with younger age ( P = .015). The associations were however insignificant in multivariate analysis. PD-L1 expression was significantly correlated with Ki-67 ( P < .001) and TP53 ( P = .02) expressions. PD-L2 expression was not correlated with either Ki-67 or TP53 expression. When grouped as combined expression (both negative vs. either positive), PD-L1/PD-L2 expression was associated with earlier recurrence ( P < .001), and was negatively correlated with expression of Ki-67 ( P < .001) but not with the expression of TP53. Conclusion: PD-L1/PD-L2 is positively expressed in chondrosarcoma and is associated with advanced clinical phenotype. PD-L1/PD-L2 expression is also associated with Ki-67 expression. Our results support the application of immune checkpoint blockade in chondrosarcoma.