University of Oulu

Almangush, A., Heikkinen, I., Mäkitie, A., Coletta, R., Läärä, E., Leivo, I., Salo, T. (2017) Prognostic biomarkers for oral tongue squamous cell carcinoma: a systematic review and meta-analysis. British Journal of Cancer, 117 (6), 856-866. doi:10.1038/bjc.2017.244

Prognostic biomarkers for oral tongue squamous cell carcinoma : a systematic review and meta-analysis

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Author: Almangush, Alhadi1,2,3; Heikkinen, Ilkka1,2; Mäkitie, Antti A4;
Organizations: 1Department of Pathology, University of Helsinki
2Department of Oral and Maxillofacial Diseases, University of Helsinki
3Institute of Dentistry, University of Misurata
4Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital and University of Helsinki
5Department of Oral Diagnosis, School of Dentistry, State University of Campinas
6Department of Mathematical Sciences and Statistics, University of Oulu
7Department of Pathology, University of Turku
8Department of Pathology, HUSLAB, Helsinki University Hospital
9Department of Diagnostics and Oral Medicine, Research Group of Cancer Research and Translational Medicine, Medical Faculty, University of Oulu
10Medical Research Center, Oulu University Hospital
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.6 MB)
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Language: English
Published: Springer Nature, 2017
Publish Date: 2018-07-27


Background: Identifying informative prognostic biomarkers for oral tongue squamous cell carcinoma (OTSCC) is of great importance in order to better predict tumour behaviour and to guide treatment planning. Here, we summarise existing evidence regarding immunohistochemical prognostic biomarkers for OTSCC.

Methods: A systematic search of the literature was performed using the databases of Scopus, Ovid Medline, Web of Science and Cochrane Library. All studies which had investigated the prognostic significance of immunohistochemical biomarkers in OTSCC during the period from 1985 to 2015 were retrieved. For the five most often evaluated biomarkers a random-effects meta-analysis on overall survival was performed, including those studies that provided the necessary statistical results.

Results: A total of 174 studies conducted during the last three decades were found, and in these 184 biomarkers were evaluated for the prognostication of OTSCC. The five biomarkers most frequently assessed were p53, Ki-67, p16, VEGFs and cyclin D1. In the meta-analyses, the most promising results of the prognostic power for OTSCC were obtained for cyclin D1. For studies of VEGF A and C the results were equivocal, but the pooled analysis of VEGF A separately showed it to be a useful prognosticator for OTSCC. There was no sufficient evidence to support p53, Ki-67 and p16 as prognostic biomarkers for OTSCC. Limitations in the quality of the published studies (e.g., small cohorts, lack of compliance with REMARK guidelines) are widespread.

Conclusions: Numerous biomarkers have been presented as useful prognosticators for OTSCC, but the quality of the conduct and reporting of original studies is overall unsatisfactory which does not allow reliable conclusions. The value of two biomarkers (VEGF-A and cyclin D1) should be validated in a multicentre study setting following REMARK guidelines.

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Series: British journal of cancer
ISSN: 0007-0920
ISSN-E: 1532-1827
ISSN-L: 0007-0920
Volume: 117
Issue: 6
Pages: 856 - 866
DOI: 10.1038/bjc.2017.244
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3122 Cancers
Funding: This article was supported by grants of Finnish Dental Society (Alhadi Almangush and Ilkka Heikkinen), the Helsinki University Hospital Research Fund (Antti Mäkitie and Tuula Salo), the Maritza and Reino Salonen Foundation (Ilmo Leivo), the Sigrid Juselius Foundation and the Finnish Cancer Society (Tuula Salo).
Copyright information: This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License.