Prognostic significance of PD-L1 protein expression and copy number gains in locally advanced cervical cancer

Abstract

Background: Although immune checkpoint inhibitors against programmed death-1 (PD-1) and its ligand (PD-L1) have demonstrated promising results in several solid malignancies, including cervical cancer, there are some limitations to using PD-L1 immunohistochemical expression as a predictive biomarker for selecting patients who may benefit from such therapy. Objective: To examine the protein expression and genetic status of PD-L1 with clinical outcomes in locally advanced cervical cancer. Methods: We investigated the PD-L1 gene copy number gains assessed by fluorescence in situ hybridization (FISH) and PD-L1 expression using immunohistochemistry in 123 patients with locally advanced cervical cancers between December 2008 and December 2016. Results: The prevalence of PD-L1 immunohistochemical expression was detected in 103/123(83%) cases. PD-L1 gene amplification and polysomy were detected in 7% and 40% of cases, respectively. PD-L1 gene amplification and polysomy were associated with positive PD-L1 immunostaining (score 1+ to 3+) in 88% and 68% of cases, respectively. Clinically, PD-L1 immunopositivity was associated with parametrial invasion at diagnosis. In contrast, PD-L1 polysomy was associated with parametrial invasion and FIGO stages III-IV, whereas PD-L1 amplification was associated with nodal metastasis. In multivariate analysis, PD-L1 amplification was predictive of worse RFS (HR, 5.68; 95%CI, 1.98-16.28; p = 0.001), whereas PD-L1 polysomy was predictive of worse LRR (HR, 4.13; 95%CI, 1.63-10.49; p = 0.003). PD-L1 immunohistochemical expression was not associated with worse outcomes in Cox models. Conclusions: Our results showed that an increase in PD-L1 gene copy number could be a novel prognostic and possible predictive biomarker for anti-PD-1/PD-L1 therapy in locally advanced cervical cancer.