PO.ET06.06 · 实验与分子治疗

肿瘤细胞 ICAM-1 表达在许多肿瘤类型中常见，并在肾细胞癌中与不良肿瘤表型相关

Tumor cell ICAM-1 expression is frequent in many tumor entities and linked to unfavorable tumor phenotype in renal cell carcinomas

编号 7226 展板 18 时间 4/22 09:00–12:00 区域 Section 18 主讲 Clara von Bargen, MD

分会场 Tumor Diagnostics, Prognostics, and Therapeutic Outcomes

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作者与单位 Authors & Affiliations

Clara von Bargen¹, Finn Wickel¹, Katharina Möller¹, Florian Lutz¹, Florian Viehweger¹, Georgia Makrypidi-Fraune¹, Martina Kluth¹, Claudia Hube-Magg¹, Christina Tsourlakis¹, Christian Bernreuther¹, Guido Sauter¹, Andreas H Marx², Ronald Simon¹, Stefan Steurer¹, Christoph Frauen¹, Nina Schraps¹, Fiete Gehrisch¹, Viktoria Chirico¹, Bertram Veith¹, Clara Luehr¹, Cosima Völkel¹, Morton Freytag¹, Natalia Gorbokon¹, Maximilian Lennartz¹, Eike C. Burandt¹, Anne Menz¹, Till Krech¹

¹University Medical Center Hamburg-Eppendorf, Hamburg, Germany,²Academic Hospital Fuerth, Fürth, Germany

摘要 Abstract

中文摘要

细胞间黏附分子 1 (ICAM-1；CD54) 是一种跨膜糖蛋白，在免疫监视、炎症、细胞信号传导和凋亡过程中发挥作用。ICAM-1 被认为是癌症中的干性标志物，常在癌细胞上表达。它可以通过与免疫细胞和细胞外基质的相互作用调节抗癌免疫反应或促进转移。由于其表面表达，ICAM-1 也正被作为治疗靶点进行探索。为更好地了解 ICAM-1 在不同癌症类型中肿瘤细胞上的表达作用，研究者采用免疫组织化学 (IHC) 对含有来自 105 种不同肿瘤类型的 5,946 份样本的组织微阵列 (TMA) 进行了 ICAM-1 分析。105 个肿瘤类别中共有 85 个在至少一例中显示出 ICAM-1 表达，70 个肿瘤类别包含至少一例强阳性病例。强 ICAM-1 阳性最常见于几种淋巴瘤亚型 (高达 98.0%)、转移性恶性黑色素瘤 (87.7%)、透明细胞肾细胞癌 (ccRCC；79.8%)、透明细胞 (小管) 乳头状 RCC (75.0%)，阴茎 (68.5%)、口腔 (62.8%)、食管 (56.7%)、咽 (54.5%)、喉 (54.0%)、肛管 (53.4%)、膀胱 (47.6%)、子宫颈 (46.3%) 和外阴 (43.0%) 的鳞状细胞癌，肝细胞癌 (55.3%)，膀胱肌层浸润性尿路上皮癌 (47.4%)，乳头状 RCC (pRCC；40.6%)，肝胆管癌 (27.3%)，肠型胃腺癌 (25.7%)，以及浆液性高级别卵巢癌 (25.4%)。在 1,337 例可评估的 ccRCC 中，ICAM-1 阳性 79.7% 为强，11.7% 为中等，6.7% 为弱，1.9% 缺失。高 ICAM-1 表达与不良 ISUP 分级 (p<0.0001)、晚期 pT 分期 (p<0.0001)、高 UICC 分期 (p=0.0002) 和远处转移 (M1，p=0.0181) 相关。在 370 例 pRCC 中，ICAM-1 阳性 40.0% 为强，21.1% 为中等，25.9% 为弱，13.0% 缺失。高 ICAM-1 阳性与不良 ISUP 分级 (p<0.0001) 相关，也倾向于与高 pT 分期 (p=0.0861) 和 UICC 分期 (p=0.0890) 相关。结论认为，肿瘤细胞上的 ICAM-1 表达在许多癌症类型中常见。高 ICAM-1 表达在 RCC 中与不良肿瘤特征相关，支持 ICAM-1 表达在癌症进展中发挥作用的观点。

查看英文原文 English abstract

Intercellular Adhesion Molecule 1 (ICAM-1; CD54) is a transmembranous glycoprotein with roles in immune surveillance, inflammation, cell signaling, and apoptotic processes. ICAM-1 is considered a stemness marker in cancer which is often expressed on cancer cells. It can modulate anti-cancer immune response or facilitate metastasis through interactions with immune cells and the extracellular matrix. Because of its surface expression, ICAM-1 is also being explored as a therapeutic target. To better comprehend the role of ICAM-1 expression on tumor cells in different cancer types, ICAM-1 was analyzed by immunohistochemistry (IHC) on tissue microarrays (TMAs) containing 5,946 samples from 105 different tumor types. A total of 85 of 105 tumor categories showed ICAM-1 expression in at least one case, and 70 tumor categories contained at least one strongly positive case. Strong ICAM-1 positivity was most seen in several subtypes of lymphomas (up to 98.0%), metastatic malignant melanoma (87.7%), clear cell renal cell carcinoma (ccRCC; 79.8%), clear cell (tubulo) papillary RCC (75.0%), squamous cell carcinomas of the penis (68.5%), oral cavity (62.8%), esophagus (56.7%), pharynx (54.5%), larynx (54.0%), anal canal (53.4%), urinary bladder (47.6%), cervix (46.3%), and the vulva (43.0%), hepatocellular carcinoma (55.3%), muscle-invasive urothelial carcinoma of the bladder (47.4%), papillary RCC (pRCC; 40.6%), cholangiocarcinoma of the liver (27.3%), intestinal type gastric adenocarcinoma (25.7%), and in serous high-grade ovarian carcinoma (25.4%). Within 1,337 evaluable ccRCCs, ICAM-1 positivity was considered strong in 79.7%, moderate in 11.7%, weak in 6.7%, and absent in 1.9%. High ICAM-1 expression was associated with unfavorable ISUP grade (p<0.0001), advanced pT stage (p<0.0001), high UICC stage (p=0.0002), and distant metastasis (M1, p=0.0181). Within 370 pRCCs, ICAM-1 positivity was strong in 40.0%, moderate in 21.1%, weak in 25.9%, and absent in 13.0%. High ICAM-1 positivity was associated with poor ISUP grade (p<0.0001) and also tended to correlate with high pT stage (p=0.0861) and UICC stage (p=0.0890). It is concluded that ICAM-1 expression on tumor cells occurs commonly in many cancer entities. That high ICAM-1 expression was linked to unfavorable tumor features in RCCs supports the concept of a role of ICAM-1 expression for cancer progression.

利益披露 Disclosure

C. von Bargen, None.. F. Wickel, None.. K. Möller, None.. F. Lutz, None.. F. Viehweger, None.. G. Makrypidi-Fraune, None.. M. Kluth, None.. C. Tsourlakis, None.. C. Bernreuther, None. G. Sauter, ardoci The mouse monoclonal antibody, ARX-604 was provided by ardoci GmbH, Hamburg, Germany (owned by a family member of GS). A. Marx, None.. R. Simon, None.. S. Steurer, None.. C. Frauen, None.. F. Gehrisch, None.. V. Chirico, None.. B. Veith, None.. C. Luehr, None.. C. Völkel, None.. M. Freytag, None.. N. Gorbokon, None.. E. C. Burandt, None.. A. Menz, None.. T. Krech, None.

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