Differential expression of haematopoietic prostaglandin D synthase by POU2F3‑positive tuft cells in conventional bilayered oncocytic and metaplastic epithelia of Warthin tumours

Hosomi,Kenta; Sato,Akira; Ishida,Mitsuaki; Nakanishi,Kensuke; Terada,Tetsuya; Haginomori,Shin-Ichi; Hirose,Yoshinobu; Fujimori,Ko

doi:10.3892/mmr.2025.13624

Differential expression of haematopoietic prostaglandin D synthase by POU2F3‑positive tuft cells in conventional bilayered oncocytic and metaplastic epithelia of Warthin tumours

Authors:
- Kenta Hosomi
- Akira Sato
- Mitsuaki Ishida
- Kensuke Nakanishi
- Tetsuya Terada
- Shin-Ichi Haginomori
- Yoshinobu Hirose
- Ko Fujimori
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Affiliations: Department of Pathobiochemistry, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka 569‑1094, Japan, Department of Pathology, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka 569‑8686, Japan, Department of Otolaryngology and Head and Neck Surgery, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka 569‑8686, Japan
Published online on: July 17, 2025 https://doi.org/10.3892/mmr.2025.13624
Article Number: 259
Copyright: © Hosomi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Warthin tumours (WT), the second most common benign salivary gland tumour, are histopathologically composed of bilayered oncocytic epithelial cells with occasional metaplastic epithelium. Tuft cells, which are chemosensory epithelial cells, are present in WT. Tuft cells serve various roles by producing physiologically active substances, such as prostaglandins (PGs). PGD2 released from tuft cells is crucial for tissue repair and inhibiting pancreatic carcinogenesis. However, whether or not tuft cells in WT produce PGD2 has not yet been elucidated. The present study aimed to investigate the production of PGD₂ in POU class 2 homeobox 3 (POU2F3; a specific tuft cell marker)‑positive cells of WT and normal salivary glands. Consecutive patients with WT who underwent surgical resection were selected. Dual immunohistochemical staining for POU2F3 and haematopoietic PGD synthase (H‑PGDS) was performed. The present study included 28 patients with WT of the parotid gland (all male patients; median age, 68 years). The conventional bilayered oncocytic epithelium was present in all tumours; squamous metaplastic epithelium and conventional bilayered oncocytic epithelium were observed in 16 patients. Dual immunohistochemical analysis revealed that POU2F3+/H‑PGDS‑ cells were exclusively present in the striated duct of the normal salivary gland, and abundant POU2F3‑positive tuft cells were observed in both the conventional bilayered oncocytic and metaplastic squamous epithelia of WT. The median ratio of POU2F3‑positive cells expressing H‑PGDS was significantly higher in the conventional oncocytic epithelium (89.9%) than in the metaplastic squamous epithelium (10.6%) of WT (P=0.00044). The present results suggest a link between tissue injury to the striated duct and the pathogenesis of WT, and that PGD₂ released from POU2F3‑positive cells in the conventional bilayered oncocytic epithelium is associated with ongoing tissue injury. Further studies are warranted to clarify the function of tuft cells in WT and gain deeper insights into the pathogenesis of WT.

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