PO.ET06.06 · 实验与分子治疗

Nectin-4在多种不同癌症类型中丰富表达

Nectin-4 expression is abundant in many different cancer entities

编号 7219 展板 11 时间 4/22 09:00–12:00 区域 Section 18 主讲 Elena Bady, MS

分会场 Tumor Diagnostics, Prognostics, and Therapeutic Outcomes

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作者与单位 Authors & Affiliations

Clara Luehr¹, Pia Lemcke¹, Katharina Möller¹, Florian Lutz¹, Florian Viehweger¹, Georgia Makrypidi-Fraune¹, Martina Kluth¹, Claudia Hube-Magg¹, Nina Schraps¹, Fiete Gehrisch¹, Christian Bernreuther¹, Guido Sauter¹, Andreas H Marx², Ronald Simon¹, Stefan Steurer¹, Christoph Fraune¹, Viktoria Chirico¹, Till S. Cauditz¹, Bertram Veit¹, Clara Von Bargen¹, Cosima Völkel¹, Morton Freytag¹, Nathalia Gorbokon¹, Maximilian Lennartz¹, Eike C. Burandt¹, Anne Menz¹, Till Krech¹, Maria C. Tsourlakis¹, Sarah Minner¹

¹Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany,²Department of Pathology, Academic Hospital Fuerth, Fuerth, Germany

摘要 Abstract

中文摘要

Nectin-4是一种I型跨膜蛋白，在不依赖钙的细胞间黏附中起关键作用，并关键性地参与多条信号通路，包括PI3K/AKT和JAK2-STAT5a通路。基于这些相互作用，Nectin-4参与调节肿瘤细胞的迁移、黏附和增殖。在多种癌症类型中，Nectin-4阳性癌症被描述为预后不良。目前Nectin-4的重要性大部分来自于其作为enfortumab vedotin（EV）药物靶点的作用，该药已获FDA批准用于晚期尿路上皮癌。EV和多种其他抗Nectin-4药物目前正在膀胱癌以及多种其他肿瘤类型的临床试验中接受研究。为更好地理解Nectin-4表达在不同癌症类型中的流行情况，我们通过免疫组化（IHC）对包含来自43种不同肿瘤类型的2,418个样本的组织微阵列（TMA）进行了Nectin-4分析。43个肿瘤类别中共有35个至少有一例显示Nectin-4表达，22个肿瘤类别至少含有一例强阳性病例。中等或强的Nectin-4阳性最常见于皮肤基底细胞癌（50.0%）、喉鳞状细胞癌（45.8%）、外阴（44.3%）、肛管（41.0%）、阴茎（39.0%）、口底（36.5%）、皮肤（32.5%）、咽（27.6%）、子宫颈（24.4%）、阴道（23.3%）、食管（20.0%）和肺（14.5%）的鳞状细胞癌，肌层浸润性尿路上皮癌（39.1%），卵巢透明细胞癌（33.3%），肺腺癌（22.9%），卵巢子宫内膜样癌（17.2%），乳腺小叶癌（16.7%），非特殊类型浸润性乳腺癌（13.3%），子宫（10.5%）和卵巢（6.3%）癌肉瘤，胰腺导管腺癌（9.9%），卵巢黏液癌（9.1%），弥漫型（5.6%）和肠型（2.9%）胃腺癌，以及前列腺腺癌（2.6-4.3%）。从这些数据得出结论，Nectin-4表达常见于广泛的不同癌症类型中。因此，抗Nectin-4癌症药物可能在膀胱癌之外的多种应用中适用。

查看英文原文 English abstract

Nectin-4 is a type I transmembrane protein with a crucial role in calcium-independent cell-cell adhesion and a critical involvement in several signaling pathways including the PI3K/AKT and the JAK2-STAT5a pathways. Based on these interactions, Nectin-4 is involved in the regulation of migration, adhesion, and proliferation of tumor cells. In several cancer entities, unfavorable prognosis has been described for Nectin-4 positive cancers. Most of the current significance of Nectin-4 is driven by its role as a drug target for enfortumab vedotin (EV) which has been FDA approved for advanced urothelial carcinoma. EV and several other anti-Nectin-4 drugs are currently being investigated in clinical trials on bladder cancer as well as in several other tumor entities. To better comprehend the prevalence of Nectin-4 expression in different cancer types, Nectin-4 was analyzed by immunohistochemistry (IHC) on tissue microarrays (TMAs) containing 2,418 samples from 43 different tumor types. A total of 35 of 43 tumor categories showed Nectin-4 expression in at least one case, and 22 tumor categories contained at least one strongly positive case. A moderate or strong Nectin-4 positivity was most seen in basal cell carcinoma of the skin (50.0%), squamous cell carcinomas of the larynx (45.8%), vulva (44.3%), anal canal (41.0%), penis (39.0%), floor of the mouth (36.5%), skin (32.5%), pharynx (27.6%), uterine cervix (24.4%), vagina (23.3%), esophagus (20.0%), and the lung (14.5%), muscle-invasive urothelial carcinoma (39.1%), clear cell carcinoma of the ovary (33.3%), pulmonary adenocarcinoma (22.9%), endometrioid carcinoma of the ovary (17.2%), lobular carcinoma of the breast (16.7%), invasive breast carcinoma of no special type (13.3%), carcinosarcoma of the uterus (10.5%) and the ovary (6.3%), ductal adenocarcinoma of the pancreas (9.9%), mucinous carcinoma of the ovary (9.1%), gastric adenocarcinoma of diffuse (5.6%) and intestinal type (2.9%), and prostatic adenocarcinoma (2.6-4.3%). It is concluded from these data that Nectin-4 expression occurs commonly in a broad range of different cancer entities. Thus, anti-Nectin-4 cancer drugs may be applicable in multiple applications beyond bladder cancer.

利益披露 Disclosure

C. Luehr, None.. P. Lemcke, None.. K. Möller, None.. F. Lutz, None.. F. Viehweger, None.. G. Makrypidi-Fraune, None.. M. Kluth, None.. C. Hube-Magg, None.. N. Schraps, None.. F. Gehrisch, None.. C. Bernreuther, None. G. Sauter, ms Validated Antibodies GmbH The rabbit recombinant monoclonal nectin-4 antibody, MSVA-904M was provided by MS Validated Antibodies GmbH, Hamburg, Germany (owned by a family member of GS).. A. Marx, None.. R. Simon, None.. S. Steurer, None.. C. Fraune, None.. V. Chirico, None.. T. S. Cauditz, None.. B. Veit, None.. C. Von Bargen, None.. C. Völkel, None.. M. Freytag, None.. N. Gorbokon, None.. M. Lennartz, None.. E. C. Burandt, None.. A. Menz, None.. T. Krech, None.. M. C. Tsourlakis, None.. S. Minner, None.

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