Heterogeneous Profile of ROR1 Protein Expression across Tumor Types

Our plain-English summary of Heterogeneous Profile of ROR1 Protein Expression across Tumor Types, by M.G. Raso, E. Barrientos Toro, K. Evans, et al (Cancers, 2024).

The study

• Authors: M.G. Raso, E. Barrientos Toro, K. Evans, Y. Rizvi, R. Lazcano, A. Akcakanat, P. Sini, F. Trapani, E.J. Madlener, L. Waldmeier, A. Lazar, F. Meric-Bernstam
• Journal: Cancers
• Published: 2024;16(10)
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This laboratory study measured how often tumors carry ROR1, a protein drug developers are targeting. It did not study asbestos or any exposure. Samples from 1142 patient tumors and 140 tumors grown in mice from patient tissue, at MD Anderson Cancer Center, were machine-stained and assessed by pathologists. A tumor counted as positive if more than 1% of its cells stained. Mesothelioma had the highest rate: the table lists 22 of 26 cases (84.6%) positive, though the text writes this as 22 of 25, which does not equal 84.6%. Using a cut-off of 146, the median staining score, 56% (14 of 25) were positive. Of the mesotheliomas, 16 were pleural, 5 peritoneal and 4 at other sites. Next came liposarcoma (36.1%), gastrointestinal stromal tumors (33.3% of 12) and uterine endometrioid carcinoma (28.9% of 45). Other tumor types ranged from 0.98% to 13.5% positive. Gastric adenocarcinoma, rhabdomyosarcoma and mesenchymal chondrosarcoma showed none. Mouse-grown tumors showed higher expression overall. The authors concluded that ROR1 may be a new treatment target for mesothelioma. They noted that using small tissue samples may have underestimated expression.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory immunohistochemistry (tissue staining) study of tumor tissue microarrays, using an automated stainer, with slides assessed by pathologists
• Who was studied: 1142 patient tumor cases of many histologic types and 140 patient-derived xenografts (tumors grown in mice), from MD Anderson Cancer Center tissue resources
• Exposure: No asbestos or other environmental or occupational exposure was studied. The study measured ROR1 protein in tumor tissue.
• Main results:
  • Mesothelioma, Table 1: 22 of 26 cases (84.6%) had ROR1 in more than 1% of tumor cells
  • Mesothelioma, text: 84.6% is given as 22/25, a fraction that does not equal 84.6%. 56% (14/25) is given for a cut-off of 146 based on the median H-score.
  • Mesothelioma sites: 16 cases pleural, 5 peritoneal, 4 other locations
  • Mesothelioma subtypes: 18 epithelioid, 6 biphasic and 1 sarcomatoid case. The single sarcomatoid case showed higher expression than the other variants.
  • In mesothelioma, the average percentage of ROR1-positive tumor cells was 68.3% and the average H-score was 143.08
  • Liposarcoma: 36.1% of 133 cases positive
  • Gastrointestinal stromal tumors: 33.3% of 12 cases positive
  • Uterine endometrioid carcinoma: 28.9% of 45 cases positive
  • Other tumor types ranged from 0.98% to 13.5% of cases positive
  • Gastric adenocarcinoma, rhabdomyosarcoma and mesenchymal chondrosarcoma showed no ROR1 expression
  • Tumors grown in mice (patient-derived xenografts) showed higher expression overall than patient specimens of the same tumor types
• The authors' conclusion: The authors concluded that ROR1 expression was low in most tumor types, and that ROR1 may be a novel therapeutic target for mesothelioma.
• Limitations the authors state:
  • Using tissue microarrays (small tissue cores) may have underestimated ROR1 expression in tumors with uneven expression
  • The study did not test all tumor types reported to be ROR1-positive, notably hematologic tumors

Topics

Medical terms in this study, explained in our Lexicon: Immunohistochemistry, Mesothelioma, Carcinoma, Sarcoma, Adenocarcinoma.

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