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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
  • View Affiliations / Copyright

    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
    Copyright: © Hosomi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 259
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    Published online on: July 17, 2025
       https://doi.org/10.3892/mmr.2025.13624
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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.
View Figures

Figure 1

Histopathological features of Warthin
tumours of the parotid gland. (A) Well-circumscribed
papillary-cystic proliferation (black arrows) surrounded by the
non-neoplastic parotid gland tissue was observed. Rich lymphoid
stroma was present around the epithelial cells, and a lymphoid
follicle was also observed (red arrow) (haematoxylin and eosin;
magnification, ×40). (B) Conventional bilayered epithelial cells
comprised inner columnar and outer cuboidal cells (black arrows)
surrounded by dense lymphoid aggregates with a germinal centre (red
arrow). These epithelial cells had rich granular eosinophilic
cytoplasm and lacked nuclear atypia (haematoxylin and eosin;
magnification, ×400). (C) Transition from the conventional
bilayered oncocytic epithelium (left side) to squamous metaplasia
(right side; black arrows). Lymphoid follicles with germinal
centres were also present around the epithelial cells (red arrow)
(haematoxylin and eosin; magnification, ×200). (D) Metaplastic
squamous cells had no nuclear atypia (black arrows) and were
surrounded by rich lymphoid stroma accompanying a lymphoid follicle
(red arrow) (haematoxylin and eosin; magnification, ×400).

Figure 2

Immunohistochemical features of WT of
the parotid gland examined using dual immunohistochemical staining
for POU2F3 (brown) and H-PGDS (red). (A) A few
POU2F3+/H-PGDS− cells were present in the
striated duct (median, 3 cells in five high-power fields; brown
arrows) but not in the acinus of the normal parotid glands
(magnification, ×400). (B) No POU2F3+/H-PGDS−
cells were noted in the excretory duct and acinus of the normal
parotid glands (magnification, ×400). (C)
POU2F3+/H-PGDS+ cells (black arrows) were
abundantly observed in the conventional bilayered oncocytic
epithelial cells, especially in the abluminal side, and a few
POU2F3−/H-PGDS+ cells (red arrows) were also
observed in the epithelial cells, especially in the abluminal side,
of the WT (magnification, ×400). (D) Numerous
POU2F3+/H-PGDS− cells (brown arrows) were
present in the metaplastic squamous epithelium of WT, and no
POU2F3+/H-PGDS+ cells were observed
(magnification, ×400). (E) Transitional area of the conventional
bilayered oncocytic epithelium (left side) and the metaplastic
squamous epithelium (right side) of WT. A number of
POU2F3+/H-PGDS+ cells (black arrows) were
present in the conventional bilayered oncocytic epithelium, while
POU2F3+/H-PGDS− cells (brown arrows) were
abundant in the metaplastic squamous epithelium.
POU2F3−/H-PGDS+ cells (red arrows) were also
observed in the conventional bilayered oncocytic epithelium
(magnification, ×400). H-PGDS, haematopoietic prostaglandin D
synthase; POU2F3, POU domain class 2 transcription factor 3; WT,
Warthin tumours.

Figure 3

Ratio of
POU2F3+/H-PGDS+ tuft cells/total
POU2F3+ cells in the conventional bilayered oncocytic
and metaplastic squamous epithelia (%). H-PGDS, haematopoietic
prostaglandin D synthase; POU2F3, POU domain class 2 transcription
factor 3.
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Copy and paste a formatted citation
Spandidos Publications style
Hosomi K, Sato A, Ishida M, Nakanishi K, Terada T, Haginomori S, Hirose Y and Fujimori K: Differential expression of haematopoietic prostaglandin D synthase by POU2F3‑positive tuft cells in conventional bilayered oncocytic and metaplastic epithelia of Warthin tumours. Mol Med Rep 32: 259, 2025.
APA
Hosomi, K., Sato, A., Ishida, M., Nakanishi, K., Terada, T., Haginomori, S. ... Fujimori, K. (2025). Differential expression of haematopoietic prostaglandin D synthase by POU2F3‑positive tuft cells in conventional bilayered oncocytic and metaplastic epithelia of Warthin tumours. Molecular Medicine Reports, 32, 259. https://doi.org/10.3892/mmr.2025.13624
MLA
Hosomi, K., Sato, A., Ishida, M., Nakanishi, K., Terada, T., Haginomori, S., Hirose, Y., Fujimori, K."Differential expression of haematopoietic prostaglandin D synthase by POU2F3‑positive tuft cells in conventional bilayered oncocytic and metaplastic epithelia of Warthin tumours". Molecular Medicine Reports 32.4 (2025): 259.
Chicago
Hosomi, K., Sato, A., Ishida, M., Nakanishi, K., Terada, T., Haginomori, S., Hirose, Y., Fujimori, K."Differential expression of haematopoietic prostaglandin D synthase by POU2F3‑positive tuft cells in conventional bilayered oncocytic and metaplastic epithelia of Warthin tumours". Molecular Medicine Reports 32, no. 4 (2025): 259. https://doi.org/10.3892/mmr.2025.13624
Copy and paste a formatted citation
x
Spandidos Publications style
Hosomi K, Sato A, Ishida M, Nakanishi K, Terada T, Haginomori S, Hirose Y and Fujimori K: Differential expression of haematopoietic prostaglandin D synthase by POU2F3‑positive tuft cells in conventional bilayered oncocytic and metaplastic epithelia of Warthin tumours. Mol Med Rep 32: 259, 2025.
APA
Hosomi, K., Sato, A., Ishida, M., Nakanishi, K., Terada, T., Haginomori, S. ... Fujimori, K. (2025). Differential expression of haematopoietic prostaglandin D synthase by POU2F3‑positive tuft cells in conventional bilayered oncocytic and metaplastic epithelia of Warthin tumours. Molecular Medicine Reports, 32, 259. https://doi.org/10.3892/mmr.2025.13624
MLA
Hosomi, K., Sato, A., Ishida, M., Nakanishi, K., Terada, T., Haginomori, S., Hirose, Y., Fujimori, K."Differential expression of haematopoietic prostaglandin D synthase by POU2F3‑positive tuft cells in conventional bilayered oncocytic and metaplastic epithelia of Warthin tumours". Molecular Medicine Reports 32.4 (2025): 259.
Chicago
Hosomi, K., Sato, A., Ishida, M., Nakanishi, K., Terada, T., Haginomori, S., Hirose, Y., Fujimori, K."Differential expression of haematopoietic prostaglandin D synthase by POU2F3‑positive tuft cells in conventional bilayered oncocytic and metaplastic epithelia of Warthin tumours". Molecular Medicine Reports 32, no. 4 (2025): 259. https://doi.org/10.3892/mmr.2025.13624
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