Programmed cell death protein 1/programmed death ligand 1 but not HER2 is a potential therapeutic target in gastric neuroendocrine carcinoma
Programmed cell death protein 1/programmed death ligand 1 but not HER2 is a potential therapeutic target in gastric neuroendocrine carcinoma
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程序性细胞死亡蛋白1/程序性死亡配体1而非HER2是胃神经内分泌癌的潜在治疗靶点
DOI：
10.1111/his.14230
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发表时间：
2020
期刊：
影响因子：
6.4
通讯作者：
Ushiku Tetsuo
中科院分区：
文献类型：
--
作者：
Yamashita Satoshi;Abe Hiroyuki;Kunita Akiko;Yamashita Hiroharu;Seto Yasuyuki;Ushiku Tetsuo
胃神经内分泌癌（NEC）是一种少见的侵袭性肿瘤，预后差.我们的目的是研究胃NEC中HER 2和程序性死亡配体1（PD-L1）的表达谱，以测试靶向这些分子的药物的潜在适用性。方法和结果在25个胃NEC中评估HER 2和PD-L1的表达水平，包括10个纯NEC和15个混合腺癌-NEC，并用联合阳性评分（CPS）来评估PD-L1表达。同时分析了p53、Rb蛋白和错配修复蛋白的表达水平与临床病理特征的关系。25例病例中的18例（72%）显示PD-L1 CPS ≥ 1，既往显示与帕博利珠单抗缓解相关。浸润边缘的淋巴结转移阳性和肿瘤浸润淋巴细胞（TIL）水平低与PD-L1 CPS < 1显著相关。所有病例的NEC组分均为HER 2阴性，而在15例混合腺癌-NEC中的6例（40%）腺癌组分中观察到HER 2阳性。分别在4例（16%）、17例（68%）和9例（36%）病例中观察到错配修复缺陷、p53表达突变模式和Rb表达缺失，尽管这些改变与PD-L1 CPS或其他临床病理特征无关。而PD-1/PD-L1通路是胃NEC的潜在治疗靶点，因为该亚型中PD-L1 CPS ≥ 1的患病率相对较高。
AimsGastric neuroendocrine carcinoma (NEC) is a rare and aggressive subtype with a poor prognosis. We aim to investigate expression profiles of HER2 and programmed death ligand 1 (PD‐L1) in gastric NEC to test the potential applicability of drugs targeting these molecules.Methods and resultsExpression levels of HER2 and PD‐L1 were evaluated in 25 gastric NECs, including 10 pure NECs and 15 mixed adenocarcinoma–NECs, and a combined positive score (CPS) was used to evaluate PD‐L1 expression. The correlations of expression levels with both clinicopathological features and the expression of p53, retinoblastoma protein (Rb) and mismatch repair proteins were also analysed. Eighteen of the 25 (72%) cases showed a PD‐L1 CPS of ≥ 1, which was previously shown to be associated with response to pembrolizumab. Positive nodal metastasis and low tumour‐infiltrating lymphocyte (TIL) levels at the invasive margin were significantly associated with a PD‐L1 CPS of < 1. The NEC component was HER2‐negative in all cases, whereas HER2 positivity was observed in the adenocarcinoma component of six of 15 (40%) mixed adenocarcinoma–NECs. Mismatch repair deficiency, a mutant pattern of p53 expression and loss of Rb expression were observed in four (16%), 17 (68%) and nine (36%) cases, respectively, although these alterations were not associated with the PD‐L1 CPS or other clinicopathological characteristics.ConclusionsHER2 is unlikely to be an effective target in gastric NEC owing to the lack of HER2 expression, whereas the PD‐1/PD‐L1 pathway is a potential therapeutic target for gastric NEC because of the relatively high prevalence of a PD‐L1 CPS of ≥ 1 in this subtype.
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影响因子：
64.8
作者：
Herbst RS;Soria JC;Kowanetz M;Fine GD;Hamid O;Gordon MS;Sosman JA;McDermott DF;Powderly JD;Gettinger SN;Kohrt HE;Horn L;Lawrence DP;Rost S;Leabman M;Xiao Y;Mokatrin A;Koeppen H;Hegde PS;Mellman I;Chen DS;Hodi FS
通讯作者：
Hodi FS
影响因子：
2
作者：
Fujimasa, Koichiro;Ohike, Nobuyuki;Takimoto, Masafumi
通讯作者：
Takimoto, Masafumi
影响因子：
3.3
作者：
Roberts JA;Gonzalez RS;Das S;Berlin J;Shi C
通讯作者：
Shi C
影响因子：
2.8
作者：
Gurzu, Simons;Fetyko, Annamaria;Jung, Loan
通讯作者：
Jung, Loan
影响因子：
5.8
作者：
Alese, Olatunji B.;Jiang, Renjian;El-Raycs, Bassel F.
通讯作者：
El-Raycs, Bassel F.