PMID- 31586491 OWN - NLM STAT- MEDLINE DCOM- 20211228 LR - 20220531 IS - 0125-877X (Print) IS - 0125-877X (Linking) VI - 39 IP - 4 DP - 2021 Dec TI - Prognostic significance of PD-L1 protein expression and copy number gains in locally advanced cervical cancer. PG - 309-318 LID - 10.12932/AP-120419-0538 [doi] AB - 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 cer- vical 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 am- plification 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 multi- variate 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. FAU - Loharamtaweethong, Kongsak AU - Loharamtaweethong K AD - Department of Anatomical Pathology, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, 10300 Thailand. FAU - Supakatitham, Chalermpak AU - Supakatitham C AD - Department of Anatomical Pathology, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, 10300 Thailand. FAU - Vinyuvat, Songkhun AU - Vinyuvat S AD - Department of Medical Services, Institute of Pathology, Ministry of Public Health, Bangkok, 10400 Thailand. FAU - Puripat, Napaporn AU - Puripat N AD - Department of Anatomical Pathology, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, 10300 Thailand. FAU - Tanvanich, Sujitra AU - Tanvanich S AD - Department of Anatomical Pathology, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, 10300 Thailand. FAU - Sitthivilai, Unaporn AU - Sitthivilai U AD - Department of Anatomical Pathology, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, 10300 Thailand. LA - eng PT - Journal Article PL - Thailand TA - Asian Pac J Allergy Immunol JT - Asian Pacific journal of allergy and immunology JID - 8402034 RN - 0 (B7-H1 Antigen) SB - IM MH - *B7-H1 Antigen/genetics MH - DNA Copy Number Variations MH - Female MH - Humans MH - In Situ Hybridization, Fluorescence MH - Prognosis MH - *Uterine Cervical Neoplasms/genetics EDAT- 2019/10/07 06:00 MHDA- 2021/12/29 06:00 CRDT- 2019/10/07 06:00 PHST- 2019/10/07 06:00 [pubmed] PHST- 2021/12/29 06:00 [medline] PHST- 2019/10/07 06:00 [entrez] AID - 10.12932/AP-120419-0538 [doi] PST - ppublish SO - Asian Pac J Allergy Immunol. 2021 Dec;39(4):309-318. doi: 10.12932/AP-120419-0538.