Rabeia Almahmoudi1, Abdelhakim Salem1,2, Meri Sieviläinen1, Elias Sundquist3, Alhadi Almangush1,4, Sanna Toppila-Salmi5, Timo Paavonen6, Tuula Salo1,2,7,8, Ahmed Al-Samadi1. 1. Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland. 2. Department of Clinical Medicine, Clinicum, University of Helsinki, Helsinki, Finland. 3. Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland. 4. Department of Pathology, University of Helsinki, Helsinki, Finland. 5. Department of Allergy, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 6. Department of Pathology, Fimlab Laboratories, Tampere University Hospital, Tampere, Finland. 7. Medical Research Centre, Oulu University Hospital, Oulu, Finland. 8. Department of Diagnostics and Oral Medicine, Research Group of Cancer Research and Translational Medicine, Medical Faculty, University of Oulu, Oulu, Finland.
Abstract
BACKGROUND: Oral tongue squamous cell carcinoma (SCC) is characterized by early metastasis and poor prognosis. Interleukin-17F (IL-17F) plays a protective role in many tumors. However, IL-17F expression in oral tongue SCC tissue has not been investigated. METHODS: Immunostaining of 83 oral tongue SCC specimens and blinded-scoring were used to map IL-17F expression, location, and distribution. Survival curves were constructed according to Kaplan-Meier method. The Cox proportional hazard model was applied for univariate and multivariate survival analyses. RESULTS: Mast cells are the major source of IL-17F in oral tongue SCC. In multivariate analysis, only the extracellular mast cell-derived IL-17F at the tumor invasion front was associated with better disease-specific survival in patients with all-stages and early-stages of oral tongue SCC. CONCLUSION: Extracellular mast cell-derived IL-17F is antitumorigenic in oral tongue SCC. It separates patients with early-stage disease who are at high risk from patients who are at low risk. Furthermore, when analyzing tentative prognostic molecules, we conclude that in addition to the staining intensity, attention must be paid to the cellular source, distribution, and location of the molecule.
BACKGROUND:Oral tongue squamous cell carcinoma (SCC) is characterized by early metastasis and poor prognosis. Interleukin-17F (IL-17F) plays a protective role in many tumors. However, IL-17F expression in oral tongue SCC tissue has not been investigated. METHODS: Immunostaining of 83 oral tongue SCC specimens and blinded-scoring were used to map IL-17F expression, location, and distribution. Survival curves were constructed according to Kaplan-Meier method. The Cox proportional hazard model was applied for univariate and multivariate survival analyses. RESULTS: Mast cells are the major source of IL-17F in oral tongue SCC. In multivariate analysis, only the extracellular mast cell-derived IL-17F at the tumor invasion front was associated with better disease-specific survival in patients with all-stages and early-stages of oral tongue SCC. CONCLUSION: Extracellular mast cell-derived IL-17F is antitumorigenic in oral tongue SCC. It separates patients with early-stage disease who are at high risk from patients who are at low risk. Furthermore, when analyzing tentative prognostic molecules, we conclude that in addition to the staining intensity, attention must be paid to the cellular source, distribution, and location of the molecule.
Authors: Aini Hyytiäinen; Rabeia Almahmoudi; Meri Sieviläinen; Anna Maria Wirsing; Priscila Rodrigues; Inger-Heidi Bjerkli; Pirjo Åström; Sanna Toppila-Salmi; Timo Paavonen; Ricardo D Coletta; Elin Hadler-Olsen; Tuula Salo; Ahmed Al-Samadi Journal: Head Neck Pathol Date: 2020-09-21