Loharamtaweethong Kongsak, Supakatitham Chalermpak, Vinyuvat Songkhun, Puripat Napaporn, Tanvanich Sujitra, Sitthivilai Unaporn
Department of Anatomical Pathology, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, 10300 Thailand.
Department of Medical Services, Institute of Pathology, Ministry of Public Health, Bangkok, 10400 Thailand.
Asian Pac J Allergy Immunol. 2021 Dec;39(4):309-318. doi: 10.12932/AP-120419-0538.
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.
To examine the protein expression and genetic status of PD-L1 with clinical outcomes in locally advanced cer- vical cancer.
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.
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.
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.
尽管针对程序性死亡蛋白1（PD-1）及其配体（PD-L1）的免疫检查点抑制剂在包括宫颈癌在内的多种实体恶性肿瘤中已显示出有前景的结果，但将PD-L1免疫组化表达用作预测生物标志物以选择可能从此类治疗中获益的患者存在一些局限性。
研究局部晚期宫颈癌中PD-L1的蛋白表达、基因状态及其与临床结局的关系。
我们对2008年12月至2016年12月期间的123例局部晚期宫颈癌患者，采用荧光原位杂交（FISH）检测PD-L1基因拷贝数增加情况，并采用免疫组化检测PD-L1表达。
123例患者中，103例（83%）检测到PD-L1免疫组化表达。分别有7%和40%的病例检测到PD-L1基因扩增和多体性。PD-L1基因扩增和多体性分别在88%和68%的病例中与PD-L1免疫染色阳性（评分1+至3+）相关。临床上，PD-L1免疫阳性与诊断时宫旁浸润相关。相比之下，PD-L1多体性与宫旁浸润和国际妇产科联盟（FIGO）III-IV期相关，而PD-L1扩增与淋巴结转移相关。在多变量分析中，PD-L1扩增预示无复发生存期（RFS）较差（风险比[HR]，5.68；95%置信区间[CI]，1.98 - 16.28；p = 0.001），而PD-L1多体性预示局部复发率（LRR）较差（HR，4.13；95%CI，1.63 - 10.49；p = 0.003）。在Cox模型中，PD-L1免疫组化表达与较差结局无关。
我们的结果表明，PD-L1基因拷贝数增加可能是局部晚期宫颈癌抗PD-1/PD-L1治疗的一种新的预后和可能的预测生物标志物。
