PO.CL01.18 · 临床研究

annexin A4在癌症中的表达：一项涉及来自105种肿瘤实体的6,058例癌症的组织微阵列研究

Expression of annexin A4 in cancer: A tissue microarray study involving 6,058 cancers from 105 tumor entities

编号 1115 展板 25 时间 4/19 02:00–05:00 区域 Section 43 主讲 Elena Bady, MS

分会场 Early Detection Biomarkers 1

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作者与单位 Authors & Affiliations

Cosima Völkel¹, Nayma Malas¹, Fiete Gehrisch¹, Nina Schraps¹, Anne Menz¹, Florian Lutz¹, Viktoria Chirico¹, Florian Viehweger¹, David Dum¹, Ria Schlichter¹, Andrea Hinsch¹, Christoph Fraune¹, Christian Bernreuther¹, Seyma Büyücek¹, Martina Kluth¹, Claudia Hube-Magg¹, Georgia Makrypidi-Fraune¹, Katharina Möller¹, Andreas M. Luebke¹, Patrick Lebok¹, Guido Sauter¹, Maximilian Lennartz¹, Till S. Clauditz¹, Andreas H. Marx², Ronald Simon¹, Eike Burandt¹, Natalia Gorbokon¹, Maria C. Tsourlakis¹, Sarah Minner¹, Till Krech¹, Morton Freytag¹, Viktor Reiswich¹, Stefan Steurer¹

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

膜联蛋白A4（ANXA4）是钙依赖性磷脂结合蛋白膜联蛋白家族的成员。与其结合磷脂膜的能力相一致，它在与膜动力学相关的过程中发挥作用，如膜运输、囊泡聚集、膜组织和离子通道调节。ANXA4的失调可导致异常的细胞迁移、增殖和抗凋亡。ANXA4的过表达已在多种癌症类型中被描述，并与肿瘤侵袭性和治疗耐药相关联。由于其在肿瘤与正常组织中的差异性表达，ANXA4正作为一种诊断生物标志物受到研究。为进一步了解ANXA4在癌症中的作用，通过免疫组织化学（IHC）在包含来自105种不同肿瘤类型的6,058份样本的组织微阵列（TMAs）上分析了ANXA4的表达。在4,839例可分析的肿瘤中，有3,649例（75.4%）观察到ANXA4染色，其中11.3%被判定为弱阳性，17.5%为中度阳性，46.6%为强阳性。在105个肿瘤类别中，100个（95.2%）至少在一例中显示ANXA4表达，92个（87.6%）在超过50%的病例中显示ANXA4染色，90个（85.7%）包含至少一例强ANXA4阳性。强ANXA4阳性率最高的出现在Vater壶腹腺癌（100%）和胰腺导管腺癌（96.0%）、胆囊腺癌（100%）、胃腺癌（93.0-99.1%）、透明细胞型（97.7%）、乳头状型（97.4%）和嫌色细胞型（94.9%）肾细胞癌（RCC）、Brenner瘤（96.4%）、结直肠腺癌（95.0%）、卵巢透明细胞癌（94.7%）、食管腺癌（94.7%）、肾嗜酸细胞瘤（94.6%）、肝细胞癌（91.8%）、卵巢黏液性癌（90.9%）、肝内胆管癌（88.6%）、宫颈腺癌（87.0%）、子宫内膜样子宫内膜癌（76.1%）、卵巢子宫内膜样癌（66.7%）以及肾盂尿路上皮癌（66.7%）中。1,219例可评估的非特殊类型（NST）乳腺癌代表了来自单一实体的最大肿瘤亚组。在这些肿瘤中，ANXA4染色阴性者642例（52.7%），弱阳性84例（6.9%），中度阳性169例（13.9%），强阳性324例（26.6%）。与肿瘤表型的比较显示，低ANXA4表达与进展期pT分期（p<0.0001）、高恶性程度（p=0.0018）和淋巴结转移（p=0.0247）相关联。总之，我们的数据全面概述了ANXA4在癌症中的表达。它们表明，ANXA4在广泛的不同肿瘤实体中常呈高水平表达。至少在NST乳腺癌中，低水平的ANXA4表达是癌症高侵袭性的一个特征。

查看英文原文 English abstract

Annexin A4 (ANXA4) is a member of the annexin family of calcium-dependent phospholipid-binding proteins. In line with its capability to bind to phospholipid membranes, it has roles in processes related to membrane dynamics such as membrane trafficking, vesicle aggregation, membrane organization, and ion channel regulation. ANXA4 dysregulation can contribute to abnormal cell migration, proliferation, and resistance to apoptosis. ANXA4 overexpression has been described in several cancer types and has been linked to tumor aggressiveness and treatment resistance. Due to its differential expression in tumors versus normal tissues, ANXA4 is being investigated as a diagnostic biomarker. To learn more on the role of ANXA4 in cancer, ANXA4 expression was analyzed by immunohistochemistry (IHC) on tissue microarrays (TMAs) containing 6,058 samples from 105 different tumor types. ANXA4 staining was seen in 3,649 (75.4%) of the 4,839 analyzable tumors, and was considered weak in 11.3%, moderate in 17.5%, and strong in 46.6% of cases. Of 105 tumor categories, 100 (95.2%) showed ANXA4 expression in at least one case, 92 (87.6%) showed ANXA4 staining in more than 50% of cases, and 90 (85.7%) included at least one case with strong ANXA4 positivity. Highest rates of strong ANXA4 positivity occurred in adenocarcinoma of the ampulla Vateri (100%) and ductal adenocarcinoma of the pancreas (96.0%), gallbladder adenocarcinoma (100%), gastric adenocarcinoma (93.0-99.1%), clear cell (97.7%), papillary (97.4%) and chromophobe (94.9%) renal cell carcinoma (RCC), Brenner tumor (96.4%), colorectal adenocarcinoma (95.0%), clear cell carcinoma of the ovary (94.7%), adenocarcinoma of the esophagus (94.7%), oncocytoma od the kidney (94.6%), hepatocellular carcinoma (91.8%), mucinous carcinoma of the ovary (90.9%), cholangiocarcinoma of the liver (88.6%), adenocarcinoma of the cervix uteri (87.0%), endometrioid endometrial carcinoma (76.1%), endometrioid carcinoma of the ovary (66.7%), and in urothelial carcinoma of the kidney pelvis (66.7%). The 1,219 evaluable breast cancers of no specific type (NST) represented the largest subset of tumors from one entity. In these tumors, ANXA4 staining was negative in 642 (52.7%), weak in 84 (6.9%), moderate in 169 (13.9%), and strong in 324 (26.6%) cases. A comparison with tumor phenotype revealed that low ANXA4 expression was linked to advanced pT-stage (p<0.0001), high grade of malignancy (p=0.0018), and nodal metastasis (p=0.0247). In summary, our data provide a comprehensive overview on ANXA4 expression in cancer. They demonstrate, that ANXA4 is often expressed at high levels in a broad range of different tumor entities. At least in breast cancer NST, a low level of ANXA4 expression is a feature of high cancer aggressiveness.

利益披露 Disclosure

C. Völkel, None.. N. Malas, None.. F. Gehrisch, None.. N. Schraps, None.. A. Menz, None.. F. Lutz, None.. V. Chirico, None.. F. Viehweger, None.. D. Dum, None.. R. Schlichter, None.. A. Hinsch, None.. C. Fraune, None.. C. Bernreuther, None.. S. Büyücek, None.. M. Kluth, None.. C. Hube-Magg, None.. G. Makrypidi-Fraune, None.. K. Möller, None.. A. M. Luebke, None.. P. Lebok, None. G. Sauter, ardoci GmbH The mouse monoclonal Annexin A4 antibody, ARX-504 was provided by MS Validated Antibodies GmbH, Hamburg, Germany (owned by a family member of GS).. M. Lennartz, None.. T. S. Clauditz, None.. A. H. Marx, None.. R. Simon, None.. E. Burandt, None.. N. Gorbokon, None.. M. C. Tsourlakis, None.. S. Minner, None.. T. Krech, None.. M. Freytag, None.. V. Reiswich, None.. S. Steurer, None.

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