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跨肿瘤类型的ROR1蛋白表达的异质性概况。

Heterogeneous Profile of ROR1 Protein Expression across Tumor Types.

作者信息

Raso Maria Gabriela, Barrientos Toro Elizve, Evans Kurt, Rizvi Yasmeen, Lazcano Rossana, Akcakanat Argun, Sini Patrizia, Trapani Francesca, Madlener Eva Johanna, Waldmeier Lorenz, Lazar Alexander, Meric-Bernstam Funda

机构信息

Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

出版信息

Cancers (Basel). 2024 May 15;16(10):1874. doi: 10.3390/cancers16101874.

Abstract

The Wnt receptor ROR1 has generated increased interest as a cancer therapeutic target. Research on several therapeutic approaches involving this receptor is ongoing; however, ROR1 tissue expression remains understudied. We performed an immunohistochemistry analysis of ROR1 protein expression in a large cohort of multiple tumor and histologic types. We analyzed 12 anonymized multi-tumor tissue microarrays (TMAs), including mesothelioma, esophageal and upper gastrointestinal carcinomas, and uterine endometrioid carcinoma, among other tumor types. Additionally, we studied 5 different sarcoma types of TMAs and 6 patient-derived xenografts (PDX) TMAs developed from 19 different anatomic sites and tumor histologic types. A total of 1142 patient cases from different histologic types and 140 PDXs placed in TMAs were evaluated. Pathologists assessed the percentage of tumor cells in each case that were positive for ROR1 and the intensity of staining. For determining the prevalence of staining for each tumor type, a case was considered positive if >1% of its tumor cells showed ROR1 staining. Our immunohistochemistry assays revealed a heterogeneous ROR1 expression profile. A high prevalence of ROR1 expression was found in mesothelioma (84.6%), liposarcoma (36.1%), gastrointestinal stromal tumors (33.3%), and uterine endometrioid carcinoma (28.9%). Other histologic types such as breast, lung, renal cell, hepatocellular, urothelial carcinoma, and colon carcinomas; glioblastoma; cholangiocarcinoma; and leiomyosarcoma showed less ROR1 overall expression, ranging between 0.9 and 13%. No ROR1 expression was seen in mesenchymal chondrosarcoma, rhabdomyosarcoma, or gastric adenocarcinoma cases. Overall, ROR1 expression was relatively infrequent and low in most tumor types investigated; however, ROR1 expression was infrequent but high in selected tumor types, such as gastroesophageal GIST, suggesting that ROR1 prescreening may be preferable for those indications. Further, mesothelioma exhibited frequent and high levels of ROR1 expression, which represents a previously unrecognized therapeutic opportunity. These findings can contribute to the development of ROR1-targeted therapies.

摘要

Wnt受体ROR1作为一种癌症治疗靶点,已引发了越来越多的关注。目前,针对该受体的多种治疗方法的研究正在进行;然而,ROR1在组织中的表达情况仍未得到充分研究。我们对大量多种肿瘤类型和组织学类型的样本进行了ROR1蛋白表达的免疫组织化学分析。我们分析了12个匿名的多肿瘤组织微阵列(TMA),包括间皮瘤、食管和上消化道癌以及子宫内膜样癌等其他肿瘤类型。此外,我们研究了5种不同类型肉瘤的TMA以及6个患者来源的异种移植(PDX)TMA,这些TMA来自19个不同的解剖部位和肿瘤组织学类型。总共评估了来自不同组织学类型的1142例患者病例以及放入TMA中的140个PDX。病理学家评估了每个病例中ROR1阳性的肿瘤细胞百分比以及染色强度。为了确定每种肿瘤类型的染色发生率,如果>1%的肿瘤细胞显示ROR1染色,则该病例被视为阳性。我们的免疫组织化学分析揭示了ROR1表达谱的异质性。在间皮瘤(84.6%)、脂肪肉瘤(36.1%)、胃肠道间质瘤(33.3%)和子宫内膜样癌(28.9%)中发现ROR1表达的高发生率。其他组织学类型,如乳腺癌、肺癌、肾细胞癌、肝细胞癌、尿路上皮癌和结肠癌;胶质母细胞瘤;胆管癌;和平滑肌肉瘤,总体ROR1表达较少,介于0.9%至13%之间。在间充质软骨肉瘤、横纹肌肉瘤或胃腺癌病例中未观察到ROR1表达。总体而言,在大多数研究的肿瘤类型中,ROR1表达相对较少且较低;然而,在某些特定肿瘤类型中,如胃肠道间质瘤,ROR1表达虽不常见但水平较高,这表明对于这些适应症,ROR1预筛查可能更可取。此外,间皮瘤表现出频繁且高水平的ROR1表达,这代表了一个以前未被认识到的治疗机会。这些发现有助于开发针对ROR1的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f38d/11119314/42b93bcb8fc1/cancers-16-01874-g001.jpg

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