PROGNOSTIC IMPLICATIONS OF PD-L1 EXPRESSION AND LOSS OF PTEN IN PATIENTS WITH RHABDOMYOSARCOMA, EWING'S SARCOMA AND OSTEOSARCOMA.

Abstract

In children, osteosarcoma (OS), Ewing's sarcoma (ES), and rhabdomyosarcoma (RMS) are the most common sarcomas. A link between the anti-programmed death ligand-1 PD-L1 and the tumor suppressor phosphatase and tensin homologue (PTEN) expression has been described in many tumors. The aim of this work is to determine clinicopathological relationships and the possible prognostic significance of PD-L1 and PTEN expression in rhabdomyosarcoma (RMS), Ewing's sarcoma (ES), and osteosarcoma (OS). Expression of PD-L1 and PTEN were examined by immunohistochemistry in 45 archival RMS, ES, and OS cases. The positive expression of PD-L1 was found in 16.7% and 31.6% of ES and OS, respectively. The negative PD-L1 was related to a substantially longer survival in ES cases (p = 0.045), but positive PD-L1 expression was significantly associated with the increased tumor stage and vascular invasion in the OS cases (p = 0.005 and p = 0.002), respectively. On the other hand, PTEN loss was strongly associated with deep tumor, high tumor grade, and recurrence in RMS (p = 0.002, p = 0.045, and p = 0.026, respectively). However, PTEN loss was significantly absent in ES as tumor grade increased (p = 0.031). It is noteworthy that tumor recurrence, the loss of PTEN, and positive PD-L1 were all considered predictive factors in OS patients (p = 0.045, p = 0.032, and p = 0.02, respectively). In children, OS and ES have positive PD-L1 expression, which has an independent unfavorable prognostic effect and raises the possibility of using PD-L1 as a therapeutic target. OS, ES, and RMS prognosis are all predicted by PTEN loss.