Cell-in-cell phenomenon associates with aggressive characteristics and cancer-related mortality in early oral tongue can
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RESEARCH ARTICLE
Open Access
Cell-in-cell phenomenon associates with aggressive characteristics and cancerrelated mortality in early oral tongue cancer Alhadi Almangush1,2,3,4,5* , Antti A. Mäkitie2,6,7, Jaana Hagström1,8,9, Caj Haglund9,10, Luiz Paulo Kowalski11,12, Pentti Nieminen13, Ricardo D. Coletta14, Tuula Salo1,3,15 and Ilmo Leivo4
Abstract Background: Cell-in-cell structures (caused by cell cannibalistic activity) have been related to prognosis of many cancers. This is the first multi-institutional study to assess the prognostic impact of cell-in-cell structures in a large cohort of early oral tongue squamous cell carcinomas (OTSCC). Methods: A total of 308 cases from five Finnish University Hospitals and from the A.C. Camargo Cancer Center, São Paulo, Brazil, were included in this study. Cell-in-cell structures were evaluated on surgical postoperative sections that stained with hematoxylin and eosin staining. Results: We found that cell-in-cell structures associated with cancer-related mortality in univariable analysis with a hazard ratio (HR) of 2.99 (95%CI 1.52–5.88; P = 0.001). This association was confirmed in multivariable analysis (HR 2.22, 95%CI 1.12–4.44; P = 0.024). In addition, statistically significant associations were observed between the cell-incell structures and other adverse histopathologic characteristics including deep invasion (P < 0.001), high index of tumor budding (P = 0.007), worst pattern of invasion (P < 0.001), perineural invasion (P = 0.01), and stroma-rich pattern (P = 0.001). Conclusions: Our findings demonstrate a significant relationship between cell-in-cell formation and aggressive characteristics of early OTSCC. Cell-in-cell structures have a distinct impact as a novel prognostic indicator in early OTSCC and they can be easily assessed during routine pathology practice. Keywords: Cell-in-cell formation, Tongue neoplasms, Biomarkers, Mortality
* Correspondence: [email protected]; [email protected] 1 Department of Pathology, University of Helsinki, Haartmaninkatu 3 (P.O. Box 21), FIN-00014 Helsinki, Finland 2 Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holde
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