University of Oulu

Karinen, S, Hujanen, R, Salo, T, Salem, A. The prognostic influence of lymphatic endothelium–specific hyaluronan receptor 1 in cancer: A systematic review. Cancer Sci. 2022; 113: 17– 27. doi:10.1111/cas.15199

The prognostic influence of lymphatic endothelium–specific hyaluronan receptor 1 in cancer : a systematic review

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Author: Karinen, Sini1; Hujanen, Roosa1; Salo, Tuula1,2,3;
Organizations: 1Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland
2Translational Immunology Research Program (TRIMM), Research Program Unit (RPU), University of Helsinki, Helsinki, Finland
3Helsinki University Hospital (HUS), Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.6 MB)
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Language: English
Published: John Wiley & Sons, 2022
Publish Date: 2021-12-21


Lymphangiogenesis is a key process in cancer development and metastasis. Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) is a widely used marker for lymphatic endothelial cells (LEC), which also mediates immune and cancer cell migration. Recently, LYVE-1–positive tumor cells were shown to acquire LEC-like phenotype and exploit this receptor for lymphatic dissemination. Furthermore, selective targeting of LYVE-1 impaired the growth of cancer-related vasculature and reduced metastasis in vivo, signifying its role in therapeutic and prognostic applications. Although numerous studies have investigated the role of LYVE-1 in cancer, a unifying detailed review of its prognostic utility is lacking to date. Thus, we compiled and critically appraised evidence from clinical studies comprising a total of 2352 patients diagnosed with different types of cancer and using a variety of experimental approaches. Collectively, most studies revealed a significant association between LYVE-1 overexpression and dismal outcome of at least one survival estimate. Furthermore, the importance of vasculature location, intra- or peritumoral, and the influence of various lymphangiogenesis-related parameters, such as lymphatic vessel density and invasion, were discussed. However, the specificity of LYVE-1 staining is challenged by its expression in non-LEC cells, implying the need for double labelling to better estimate its prognostic significance. In conclusion, this is to our knowledge the first comprehensive systematic review on the prognostic value of LYVE-1 in cancer. More well-designed studies across different populations and the development of standardized protocols would be paramount for the consistency of LYVE-1 findings and for its potential transferability to clinical practice in future.

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Series: Cancer science
ISSN: 1347-9032
ISSN-E: 1349-7006
ISSN-L: 1347-9032
Volume: 113
Issue: 1
Pages: 17 - 27
DOI: 10.1111/cas.15199
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3122 Cancers
Funding: The authors would like to acknowledge the funders of this study: MD-PhD Program, Faculty of Medicine, University of Helsinki; Paulo Foundation; Finnish Medical Foundation; Jane and Aatos Erkko Foundation; Minerva Foundation Institute for Medical Research; Cancer Society of Finland; Sigrid Jusélius Foundation; Helsinki University Central Hospital research funds; and Oulu University Hospital MRC grant.
Copyright information: © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.