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Cancer Sci. 2019 Sep 8. doi: 10.1111/cas.14189. [Epub ahead of print]

The Prognostic Value of Blood and Lymphatic Vessel Markers in Tongue Cancer: A Systematic Review.

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Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Biomedicum Helsinki 1, 00014, Helsinki, Finland.
Translational Immunology Research Program (TRIMM), University of Helsinki, Biomedicum Helsinki 1, 00014, Helsinki, Finland.
Institute for Molecular Medicine Finland FIMM, Helsinki Institute of Life Science HiLIFE, University of Helsinki, 00014, Helsinki, Finland.
Department of Public Health, University of Helsinki, 00014, Helsinki, Finland.
Department of Mathematics and Statistics, University of Helsinki, 00014, Helsinki, Finland.
Cancer and Translational Medicine Research Unit, University of Oulu, 90014, Oulu, Finland.
Medical Research Centre, Oulu University Hospital, 90014, Oulu, Finland.
Helsinki University Hospital, 00014, Helsinki, Finland.


Tongue squamous cell carcinoma (TSCC) has a poor prognosis due to its early metastasis via blood and lymphatic vessels. We performed a systematic review to investigate the prognostic significance of blood microvessel density (MVD) and lymphatic vessel density (LVD) in TSCC patients. We conducted a systematic search in Ovid Medline, Scopus, and Cochrane libraries. All studies that evaluated the prognostic significance of MVD/LVD markers in TSCC were systematically retrieved. Our results showed that MVD/LVD markers, CD31, CD34, CD105, factor VIII, LYVE-1, and D2-40 were evaluated in TSCC patients until 28 June 2018. Six out of 13 studies reported markers that were associated with poor prognosis in TSCC. Two out of three studies suggested that a high number of D2-40+ vessels predicated low overall survival (OS); the third study reported that the ratio of D2-40+ over factor VIII+ vessels is associated with low OS. Most of the other markers had controversial results for prognostication. We found higher expression of MVD/LVD markers were commonly, but not always, associated with shorter survival in TSCC patients. It is therefore not currently possible to recommend implementation of these markers as reliable prognosticators in clinical practice. More studies (especially for D2-40) with larger patient cohorts are needed.


Biomarker; blood microvessel density; lymphatic vessel density; prognosis; tongue squamous cell carcinoma

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