Prognostic significance of PD-L1 protein expression and copy number gains in locally advanced cervical cancer
Kongsak Loharamtaweethong,1 Chalermpak Supakatitham,1 Songkhun Vinyuvat,2 Napaporn Puripat,1 Sujitra Tanvanich,1 Unaporn Sitthivilai1
1 Department of Anatomical Pathology, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
2 Department of Medical Services, Institute of Pathology, Ministry of Public Health, Bangkok, Thailand
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.
Key words: Prognosis, programmed cell death-ligand 1, protein expression, copy number status, cervical cancer,