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.
Wnt受体ROR1作为癌症治疗靶点日益受到关注。目前针对该受体的多种治疗方法正在研究中，但ROR1的组织表达情况仍未得到充分研究。我们对多种肿瘤及组织学类型的大样本进行了ROR1蛋白表达的免疫组化分析。研究涵盖12个匿名多肿瘤组织芯片，包括间皮瘤、食管及上消化道癌、子宫内膜样癌等多种肿瘤类型。此外，我们还分析了5种不同类型的肉瘤组织芯片，以及源自19个不同解剖部位和肿瘤组织学类型的6个患者来源异种移植模型组织芯片。共评估了1142例不同组织学类型的患者样本和140例组织芯片中的患者来源异种移植模型样本。病理学家评估了每个病例中ROR1阳性肿瘤细胞的百分比及染色强度。为确定各肿瘤类型的染色阳性率，将肿瘤细胞ROR1染色>1%的病例定义为阳性。我们的免疫组化检测显示ROR1表达具有异质性。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ROR1表达阳性率较高。而乳腺癌、肺癌、肾细胞癌、肝细胞癌、尿路上皮癌、结肠癌、胶质母细胞瘤、胆管癌和平滑肌肉瘤等其他组织学类型的总体ROR1表达率较低，介于0.9%至13%之间。间叶性软骨肉瘤、横纹肌肉瘤和胃腺癌病例中未检测到ROR1表达。总体而言，在大多数研究的肿瘤类型中，ROR1表达相对少见且水平较低；但在某些特定肿瘤类型（如胃食管间质瘤）中，ROR1表达虽不常见但水平较高，这表明针对这些适应症进行ROR1预筛查可能更为适宜。此外，间皮瘤表现出高频且高水平的ROR1表达，这代表了一个先前未被认识的治疗机会。这些发现有助于推动ROR1靶向疗法的开发。
Heterogeneous Profile of ROR1 Protein Expression across Tumor Types
肿瘤(癌症)患者之家