Chen Longyun, Yang Fan, Feng Ting, Wu Shafei, Li Kaimi, Pang Junyi, Shi Xiaohua, Liang Zhiyong
Department of Pathology, State Key Laboratory of Complex Severe and Rare Disease, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Front Oncol. 2021 Oct 21;11:752453. doi: 10.3389/fonc.2021.752453. eCollection 2021.
Cervical small cell neuroendocrine carcinoma (SCNC) is a rare and aggressive disease that lacks a standard treatment strategy or effective methods of targeted therapy. PD-L1 inhibitors for DNA mismatch repair system-deficient (dMMR) tumors and neurotrophin receptor tyrosine kinase (NTRK) inhibitors offer potential pan-cancer treatments.
Immunohistochemistry was employed as the main detection method, and any NTRK positive cases, identified by immunohistochemistry, were further submitted for evaluation by fluorescence hybridization (FISH) and real-time polymerase chain reaction (RT-PCR) methods.
Forty-six patients were enrolled. Positive PD-L1 expression was seen in 22 of the 43 patients (51.16%) with an average combined positive score of 6.82. PD-L1-positive patients were more likely to have a higher proliferation rate in the tumor, and they experienced less recurrence and death (p = 0.048 and 0.033, respectively) compared with the patients with negative PD-L1 expression. However, in the multivariate analysis, none of the clinical parameters was associated with the expression of PD-L1. There was no association between PD-L1 expression and disease recurrence or overall survival in the Kaplan-Meier analysis. All cases were found to be MMR-stable and lacked NTRK gene fusion. However, pan-Trk expressed in 14 (32.56%) of the 43 tested cases, but FISH and RT-PCR failed to confirm any positive fusion signals in IHC-positive cases.
PD-L1 may be an effective therapeutic target for cervical SCNC. Cervical SCNC is a MMR-stable tumor and lacks NTRK gene fusion. IHC isn't a reliable method in the detection of NTRK gene fusion in cervical SCNC.
宫颈小细胞神经内分泌癌（SCNC）是一种罕见且侵袭性强的疾病，缺乏标准治疗策略或有效的靶向治疗方法。用于DNA错配修复系统缺陷（dMMR）肿瘤的程序性死亡受体1配体（PD-L1）抑制剂和神经营养因子受体酪氨酸激酶（NTRK）抑制剂提供了潜在的泛癌治疗方法。
采用免疫组织化学作为主要检测方法，对免疫组织化学鉴定出的任何NTRK阳性病例，进一步采用荧光杂交（FISH）和实时聚合酶链反应（RT-PCR）方法进行评估。
共纳入46例患者。43例患者中有22例（51.16%）PD-L1表达阳性，平均综合阳性评分为6.82。与PD-L1表达阴性的患者相比，PD-L1阳性患者肿瘤增殖率更高，复发和死亡更少（分别为p = 0.048和0.033）。然而，在多变量分析中，没有临床参数与PD-L1表达相关。在Kaplan-Meier分析中，PD-L1表达与疾病复发或总生存期之间没有关联。所有病例均为错配修复稳定，且缺乏NTRK基因融合。然而，在43例检测病例中有14例（32.56%）泛Trk表达，但FISH和RT-PCR未能在免疫组化阳性病例中确认任何阳性融合信号。
PD-L1可能是宫颈SCNC的有效治疗靶点。宫颈SCNC是一种错配修复稳定的肿瘤，缺乏NTRK基因融合。免疫组化在检测宫颈SCNC的NTRK基因融合方面不是一种可靠的方法。
