Immunohistochemical Demonstration of Tuft Cells in Human Acinar-to-Ductal Metaplasia and Pancreatic Intraepithelial Neoplasia

<b>Background/Objectives</b>: Acinar-to-ductal metaplasia (ADM) refers to the dedifferentiation or transdifferentiation of pancreatic acinar cells. Recently, ADM has received considerable attention as a potential precursor of pancreatic tumours. Previous studies in mouse models identified tuft cells, chemosensory epithelial cells, in ADM and pancreatic intraepithelial neoplasia (PanIN), both considered precursor lesions of pancreatic ductal adenocarcinoma (PDAC), but not in PDAC. We examined the presence of tuft cells in human ADM and PanIN. <b>Methods</b>: We analysed tissue samples from 29 patients (16 women, 13 men; median age 74 years) who underwent surgical resection for pancreatic tumours. Immunohistochemical staining for the tuft cell marker, POU2F3, was used to detect tuft cells in ADM and PanIN lesions. <b>Results</b>: ADM was present in all patients. POU2F3-positive tuft cells were observed in 46.4% of ADM lesions (327/705) but not in normal pancreatic acini. The number of POU2F3-positive tuft cells per PanIN area were significantly higher in low-grade PanIN (median, 2 cells; range, 0-20 positive cells) than in high-grade PanIN (median, 0 cell; range 0-4 positive cells) (<i>p</i> = 0.0050). The percentage of POU2F3-positive tuft cells per total cells in low-grade PanIN lesions (median, 1.1%; range 0-2.5%) was also significantly higher than that in high-grade PanIN lesions (median, 0%; range 0-1.1%) (<i>p</i> = 0.0044). <b>Conclusions</b>: Our results suggest that tuft cells emerge in human pancreatic acini during ADM, possibly as part of tissue repair following injury.