Immunohistochemical analysis of immune checkpoint proteins (PD-1, PD-L1 and PD-L2) in giant cell granulomas of the jaws and giant cell tumor of bone.

OBJECTIVE

To evaluate the immunoexpression of programmed cell death protein 1 (PD-1) and programmed cell death ligands 1 (PD-L1) and 2 (PD-L2) in giant cell granulomas of the jaws (central giant cell granuloma [CGCG], peripheral giant cell granuloma [PGCG]) and giant cell tumor of bone (GCTB).

DESIGN

Thirty CGCG (15 non-aggressive and 15 aggressive), 15 PGCG, and 15 GCTB were selected. The percentages of cytoplasmic (PD-1, PD-L1, and PD-L2) and nuclear (PD-L1) staining in mononuclear cells (MC) and in non-cannibalistic (ncMGC) and cannibalistic MGC (cMGC) were determined.

RESULTS

Cytoplasmic expression of PD-1 and PD-L1 was observed in all groups, with high median percentages of positivity in ncMGC and cMGC. Compared to CGCG and PGCG, GCTB exhibited higher expression of PD-L1 in MC (p < 0.05). In ncMGC, expression of PD-1 was higher in GCTB compared to non-aggressive CGCG (p < 0.05). Similarly, higher PD-L1 immunopositivity was found in ncMGC of GCTB compared to aggressive CGCG and PGCG (p < 0.05). For all cell types, lower median percentages of PD-L2 positivity were observed in GCTB compared to CGCG and PGCG (p > 0.05). In GCTB, there was a strong positive correlation between the cytoplasmic expression of PD-L1 in MC and PD-1 in ncMGC (r = 0.535; p < 0.05). All groups exhibited low nuclear immunoexpression of PD-L1.

CONCLUSION

The results suggest the potential participation of PD-1, PD-L1, and PD-L2 in the pathogenesis of CGCG, PGCG, and GCTB. The locally aggressive behavior of GCTB could be associated with a higher osteoclastogenic and immunosuppressive microenvironment in these neoplasms.