University of Oulu

Silva, GVD, da Silva Dolens, E, Paranaíba, LMR, et al. Exploring the combination of tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding with WHO histopathological grading on early-stage oral squamous cell carcinoma prognosis. J Oral Pathol Med. 2022; 1- 8. doi:10.1111/jop.13359

Exploring the combination of tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding with WHO histopathological grading on early-stage oral squamous cell carcinoma prognosis

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Author: Silva, Gabriela Vivili Domingues1; Da Silva Dolens, Eder2,3; Paranaíba, Lívia Máris Ribeiro4;
Organizations: 1Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, Brazil
2Graduate Program in Oral Biology, School of Dentistry, University of Campinas, Piracicaba, Brazil
3School of Dentistry, University of Western Paulista (UNOESTE), Presidente Prudente, Brazil
4Department of Pathology and Parasitology, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, Brazil
5Center of Biological Sciences and of the Health, School of Dentistry, State University of Western Parana, Cascavel, Brazil
6Laboratory of Pathology and Molecular Biology, Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil
7Department of Propedeutics, School of Dentistry, Federal University of Bahia, Salvador, Brazil
8Department of Pathology, University of Turku, Turku, Finland
9Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland
10Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland
11Department of Oral and Maxillofacial Surgery, Queen Alexandra Hospital, Portsmouth, UK
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe2022122173151
Language: English
Published: John Wiley & Sons, 2022
Publish Date: 2023-09-23
Description:

Abstract

Background: While the relevance of the World Health Organization histopathological grading system as a prognostic tool for oral squamous cell carcinoma has received many critics, other histopathological features such as tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding are displaying promising results. Here, we evaluated the prognostic impact of the incorporation of tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding into World Health Organization histopathological grading for patients with oral squamous cell carcinoma.

Methods: A total of 95 patients with early-stage oral squamous cell carcinoma were enrolled in the study, and World Health Organization tumor grading, tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding were evaluated in surgical slides stained with hematoxylin and eosin. Survival analyses for cancer-specific survival and disease-free survival were performed using Cox regression models, and receiver operating characteristic curves were applied for assessment of the performance of the combinations.

Results: Tumor-stroma ratio (stroma-rich) was significantly and independently associated with both shortened cancer-specific survival and poor disease-free survival, individually and in combination with World Health Organization histopathological grading. The combination of tumor-stroma ratio with World Health Organization grading did not improve the discriminatory ability compared to tumor-stroma ratio alone. Although low tumor-infiltrating lymphocytes were associated with shortened cancer-specific survival, the association did not withstand multivariate analysis. However, in combination with World Health Organization grading, low tumor-infiltrating lymphocytes were independently associated with poor cancer-specific survival. The combination of tumor-infiltrating lymphocytes and World Health Organization histopathological grading displayed a better discrimination of poor cancer-specific survival than tumor-infiltrating lymphocytes alone, but not at a significant level.

Conclusions: Our findings support tumor-stroma ratio as a potential prognostic marker for patients with oral squamous cell carcinoma, and the incorporation of tumor-infiltrating lymphocytes into the World Health Organization grading system improves the prognostic ability of the tumor grading alone.

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Series: Journal of oral pathology & medicine
ISSN: 0904-2512
ISSN-E: 1600-0714
ISSN-L: 0904-2512
Volume: In press
DOI: 10.1111/jop.13359
OADOI: https://oadoi.org/10.1111/jop.13359
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Subjects:
Funding: This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (2018/16077-6 to Ricardo D. Coletta) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) (APQ 00205.16 to Lívia Máris Ribeiro Paranaíba). Gabriela Vivili Domingues Silva (2021/13595-9) is a research fellow supported by FAPESP.
Copyright information: © 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. This is the peer reviewed version of the following article: Silva, GVD, da Silva Dolens, E, Paranaíba, LMR, et al. Exploring the combination of tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding with WHO histopathological grading on early-stage oral squamous cell carcinoma prognosis. J Oral Pathol Med. 2022; 1- 8, which has been published in final form at http://dx.doi.org/10.1111/jop.13359. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.