University of Oulu

Sieviläinen, M., Wirsing, A.M., Hyytiäinen, A. et al. Evaluation Challenges in the Validation of B7-H3 as Oral Tongue Cancer Prognosticator. Head and Neck Pathol 15, 469–478 (2021).

Evaluation challenges in the validation of B7-H3 as oral tongue cancer prognosticator

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Author: Sieviläinen, Meri1,2; Wirsing, Anna Maria3; Hyytiäinen, Aini1,2;
Organizations: 1Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland
2Translational Immunology Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
3Department of Medical Biology, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
4Cancer Research and Translational Medicine Research Unit, University of Oulu, Oulu, Finland
5Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
6Department of Otorhinolaryngology, University Hospital of North Norway, Tromsø, Norway
7Skin and Allergy Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
8Department of Pathology, Faculty of Medicine and Health Technology and Fimlab laboratories, Tampere University and Tampere University Hospital, Tampere, Finland
9Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil
10The Public Dental Health Competence Center of Northern Norway, Tromsø, Norway
11University of Helsinki Central hospital, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.5 MB)
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Language: English
Published: Springer Nature, 2021
Publish Date: 2020-12-14


B7-H3 was the only molecule identified with prognostic potential from a recent systematic review of the prognostic value of immune checkpoints in oral cancer. We aimed to validate this finding in a multicenter international cohort. We retrospectively retrieved 323 oral tongue squamous cell carcinoma (OTSCC) samples from three different countries (Brazil, Finland, and Norway) for immunostaining and scoring for B7-H3. We evaluated tumor immunogenicity by analyzing the amount of tumor-infiltrating lymphocytes and divided the tumors into immune hot and cold. To increase the reliability of the results, both digital and manual visual scoring were used. Survival curves were constructed based on the Kaplan-Meier method, and the Cox proportional hazard model was utilized for univariate and multivariate survival analysis. B7-H3 expression was not significantly associated with overall or disease-specific survival in the whole OTSCC cohort. When divided into immune hot and cold tumors, high B7-H3 expression was significantly associated with poor disease-specific and overall survival in the immune hot group, depending on the scoring method and the country of the cohort. This was achieved only in the univariate analysis. In conclusion, B7-H3 was a negative prognosticator for OTSCC patient survival in the subgroup of immune hot tumors, and was not validated as a prognosticator in the full cohort. Our findings suggest that the immune activity of the tumor should be considered when testing immune checkpoints as biomarkers.

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Series: Head and neck pathology
ISSN: 1936-055X
ISSN-E: 1936-0568
ISSN-L: 1936-055X
Volume: 15
Pages: 469 - 478
DOI: 10.1007/s12105-020-01222-3
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: The authors acknowledge the funders of this study: Niilo Helander Foundation, Suomen Naishammaslääkärit ry, Selma and Maja-Lisa Selander’s Fund, the Sigrid Jusélius Foundation, the Cancer Society of Finland, the Oulu University Hospital MRC grant, the Helsinki University Central Hospital research funds, and Jane and Aatos Erkkos Foundation. Open access funding provided by University of Helsinki including Helsinki University Central Hospital.
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