Introduction
Intraductal papillary mucinous neoplasm (IPMN) is
the second most common pancreatic neoplasm of the surgical
specimens, because nearly 90% of adult pancreatic neoplasm are
pancreatic ductal adenocarcinomas (PDACs) and cystic and
intraductal neoplasms comprise 4-5%, in which 60% of cyst-forming
neoplasms are IPMNs (1).
Population-based incidence of pancreatic cysts are around 2%, and
the incidence of IPMN is 0% in 20's, 0.2% in 30's, and 6.6% in 70's
based on abdominal ultrasound screening study (2). The other report showed that estimated
population prevalence of IPMN was 10.9% of persons aged 50 years or
older (3), but more than 80% of
IPMN have no worrisome or high-risk features, thus, most of these
patients are not for candidate for surgical resection (2,3). The
exact data of the number of IPMN patient are not available, because
most of IPMN patients are not for candidate for surgical resection.
IPMN is characterised by grossly visible intraductal papillary
proliferation of mucin-producing cells in the main pancreatic duct
and/or its branches, leading to cystic dilatation of the pancreatic
ducts by mucin accumulation (4).
Invasive carcinoma can contiguously occur with IPMN, and these
tumours are designated as IPMN-associated invasive carcinoma
(2,4). IPMN is classified into low- and
high-grade according to the highest degree of cytoarchitectural
atypia in the neoplastic cells (4). Low-grade dysplasia progresses to
high-grade dysplasia and eventually to IPMN associated with
invasive carcinoma (5). Although
IMPN frequently harbours KRAS and GNAS mutations
(60-80% and 50-70%, respectively), the detailed pathogenesis of
this tumour remains unclear (4).
Tuft cells are chemosensory epithelial cells located
on normal luminal surfaces of the respiratory and gastrointestinal
tracts and act as luminal sensors (6). These cells play various important
roles in these organs, such as in the response to parasitic or
bacterial infection and tissue injury and repair (6). Tuft cells also play a pivotal role in
tumourigenesis, and their significance in the carcinogenesis of
PDAC has been reported (7,8). Tuft cells emerge in lesions of
acinar-to-ductal metaplasia (ADM), a possible precursor lesion of
pancreatic intraepithelial neoplasm (PanIN), which are not detected
in the normal pancreatic acini of either the human or mouse
pancreas (7-9).
ADM is a regenerative process resulting from pancreatic acinar
injury and can progress to PanIN and PDAC in a mouse model
(7). DelGiorno et al
(7) clearly demonstrated that tuft
cells appeared in ADM and gradually decreased from ADM to PanIN and
that there were no tuft cells in PDAC in a Kras-induced
pancreatic tumourigenesis mouse model. They also showed that tuft
cells inhibited the development and acceleration of PanIN to PDAC
by producing prostaglandin D2 (PGD2), a lipid
mediator that suppresses inflammation and tissue repair (7). Moreover, our previous study revealed
that tuft cells emerged in human ADM lesions and that the number of
tuft cells was significantly higher in low-grade PanIN than in
high-grade PanIN in the human pancreas (8). Thus, tuft cells may play a pivotal
role in the development of PanIN lesions in both mice and humans.
However, only one report has addressed the presence of tuft cells
in IPMN. Qiu et al (10)
showed that tuft cells were present in mouse IPMN in approximately
the same number as those in PanIN and ADM and demonstrated that
these cells were also present in human IPMN lesions. However, it
remains unclear whether tuft cells present in human IPMN lesions
produce PGD2 and whether they are present in the
invasive lesions of IPMN associated with invasive carcinoma. This
study aimed to clarify the role of tuft cells in human IPMN.
Materials and methods
Patient selection
We selected consecutive patients with IPMN who
underwent surgical resection at the Department of General and
Gastroenterological Surgery of Osaka Medical and Pharmaceutical
University Hospital (Takatsuki, Japan) between January 2022 and
December 2023. Patients who received neoadjuvant chemotherapy
and/or radiation therapy were excluded, because these therapies may
have influenced the presence and/or number of tuft cells. We
assessed the information of the medical records and tissue samples
in July 2025.
This retrospective, single-institution study was
conducted in accordance with the tenets of The Declaration of
Helsinki. The study protocol was approved by the Institutional
Review Board of Osaka Medical and Pharmaceutical University
Hospital (approval no. 2023-198). All data were anonymised.
Informed consent was obtained from the patients using the opt-out
method because of the retrospective study design, as medical
records and archived samples were used with no risk to the
participants. Moreover, the present study did not include minors.
Information regarding this study, such as the inclusion criteria
and opportunity to opt out, was provided via the institutional
website (https://www.ompu.ac.jp/u-deps/path/img/file34.pdf).
Histopathological analysis
Surgically resected specimens were fixed in 10%
buffered neutral formalin, sectioned, and stained with haematoxylin
and eosin. Two researchers (KN and MI) independently evaluated the
histopathological features of all the slides.
The diagnostic criteria for IPMN are based on the
recent World Health Organization classification (4). IMPN is characterised by the
intraductal proliferation of columnar neoplastic cells with
intracytoplasmic mucin and is classified into low- and high-grade
based on the highest degree of cytoarchitectural atypia of the
neoplastic cells (4). Low-grade
IPMN is characterised by mild-to-moderate nuclear atypia and may or
may not have papillary projections and mitoses. High-grade IPMN is
characterised by severe nuclear atypia, nuclear stratification with
loss of polarity, papillary structures with irregular branches, and
numerous mitoses (4). IPMN
associated with invasive carcinoma is defined as infiltrative
neoplastic proliferation of glandular cells with or without
abundant stromal mucin deposition contiguous with IPMN (4).
Immunohistochemical analyses
Immunohistochemical staining was performed using an
autostainer (Leica Bond-MAX; Leica Biosystems GmbH), according to
the manufacturer's instructions. The BOND Polymer Refine Detection
Kit (DS9800; Leica) and BOND Polymer Refine Red Detection Kit
(DS9390; Leica) were used for dual immunohistochemical staining, as
the same method as previously reported (11). Rabbit monoclonal antibodies against
POU domain class 2 transcription factor 3 (POU2F3) (E5N2D; Cell
Signalling Technology; diluted 1:200) and rabbit polyclonal
antibodies against haematopoietic PGD synthase (H-PGDS) [(11), diluted 1:4,000] were used. In the
present study, POU2F3, also known as Oct11 or Skn1, was used to
detect human tuft cells because it is the master regulator of tuft
cell identity and is useful marker of human tuft cells (6,11,12).
PGD2 is synthesised by PGDS, and immunohistochemical
analysis of PGDS is a useful method for demonstrating
PGD2 synthesis (7,11,13,14).
H-PGDS expression has been reported in tuft cells present in the
human salivary glands and tumour lesions (11).
Squamous cells of the skin were used as positive
controls for POU2F3(15), and
placental trophoblasts were used for H-PGDS (16). These skin and placental tissues
were obtained from Osaka Medical and Pharmaceutical University
Hospital. Negative controls were prepared without primary
antibodies. Nuclear and cytoplasmic staining were recognised as
positive immunoreactivity for POU2F3 (11,15)
and H-PGDS (11,14,16),
respectively.
Two authors (KN and MI) independently evaluated the
immunohistochemical features. POU2F3+/H-PGDS+
(nuclei stained black and cytoplasm stained red),
POU2F3+/H-PGDS- (only nuclei stained brown),
and POU2F3-/H-PGDS+ cells (both nuclei and
cytoplasm stained red) were separately counted in five high-power
fields (x400) within the IPMN and invasive carcinoma regions (if
present) in each tumour and in the non-neoplastic pancreatic
tissues around the tumour.
Statistical analyses
Differences between the two groups were analysed
using the Mann-Whitney U test or Wilcoxon signed-rank test, using
Statcel 5 (OMS Ltd., Tokyo, Japan). P<0.05 was considered to
indicate a statistically significant difference.
Results
Patient and histopathological
characteristics
Table I summarises
the clinicopathological features of the study cohort. This study
included 11 women (52.4%) and 10 men (47.6%). The median age at the
time of surgery was 74 (range, 61-81 years). The tumour locations
were as follows: pancreatic head in eight (38.1%) patients and body
and tail in 13 (61.9%) patients. Eleven (52.4%), two (9.5%), and
eight (38.1%) patients had IPMN with low-grade dysplasia,
high-grade dysplasia, and IPMN associated with invasive carcinoma,
respectively.
 | Table IClinicopathological characteristics
of the present cohort (n=21). |
Table I
Clinicopathological characteristics
of the present cohort (n=21).
| Characteristic | Value |
|---|
| Median age, years
(range) | 74 (61-81) |
| Sex, n (%) | |
|
Male | 10 (47.6) |
|
Female | 11 (52.4) |
| Tumour location, n
(%) | |
|
Head | 8 (38.1) |
|
Body and
tail | 13 (61.9) |
| Tumour pathology, n
(%) | |
|
IPMN with
low-grade dysplasia | 11 (52.4) |
|
IPMN with
high-grade dysplasia | 2 (9.5) |
|
IPMN with
associated invasive carcinoma | 8 (38.1) |
Immunohistochemical
characteristics
In non-neoplastic pancreatic tissues,
POU2F3-positive tuft cells were present in the pancreatic ducts
(from the interlobular ducts to the main pancreatic ducts). The
median number of POU2F3-positive cells present in non-neoplastic
pancreatic ducts was 10 cells/5-high power fields (range, 3-28
cells). More than half of these POU2F3-positive tuft cells
expressed H-PGDS (Fig. 1A),
because the median ratio of
(POU2F3+/H-PGDS+)/[(POU2F3+/H-PGDS+)
+ (POU2F3+/H-PGDS-)] was 66.7% (range,
25-92.9%). Neither POU2F3-positive tuft cells nor H-PGDS-positive
cells were observed in the non-neoplastic acini.
![Immunohistochemical features using
dual immunohistochemical staining for POU2F3 (brown) and H-PGDS
(red). (A) In non-neoplastic pancreatic tissue, a few
POU2F3-positive tuft cells expressing H-PGDS (black arrows) are
present in the interlobular pancreatic duct. POU2F3-positive tuft
cell without H-PGDS expression (brown arrow) is also noted
(original magnification, x400). (B) In IPMN with low-grade
dysplasia, POU2F3-positive tuft cells with and without H-PGDS
expression (black and brown arrows, respectively) are observed
among the neoplastic glandular cells (original magnification,
x400). (C) In IPMN with high-grade dysplasia, POU2F3-positive tuft
cells with and without H-PGDS expression (black and brown arrows,
respectively) are observed among the neoplastic glandular cells
(original magnification, x400). (D) IPMN associated with invasive
carcinoma. In non-invasive carcinoma region, a few POU2F3-positive
tuft cells with or without H-PGDS expression (black and brown
arrows, respectively) are observed among the neoplastic glandular
cells (left lower). No POU2F3-positive tuft cells are noted in the
invasive carcinoma portion (right upper) [original magnification,
x40, x400 (inset)]. H-PGDS, haematopoietic prostaglandin D
synthase; IPMN, intraductal papillary mucinous neoplasm; POU2F3,
POU domain class 2 transcription factor 3.](/article_images/mco/25/1/mco-25-01-02955-g00.jpg) | Figure 1Immunohistochemical features using
dual immunohistochemical staining for POU2F3 (brown) and H-PGDS
(red). (A) In non-neoplastic pancreatic tissue, a few
POU2F3-positive tuft cells expressing H-PGDS (black arrows) are
present in the interlobular pancreatic duct. POU2F3-positive tuft
cell without H-PGDS expression (brown arrow) is also noted
(original magnification, x400). (B) In IPMN with low-grade
dysplasia, POU2F3-positive tuft cells with and without H-PGDS
expression (black and brown arrows, respectively) are observed
among the neoplastic glandular cells (original magnification,
x400). (C) In IPMN with high-grade dysplasia, POU2F3-positive tuft
cells with and without H-PGDS expression (black and brown arrows,
respectively) are observed among the neoplastic glandular cells
(original magnification, x400). (D) IPMN associated with invasive
carcinoma. In non-invasive carcinoma region, a few POU2F3-positive
tuft cells with or without H-PGDS expression (black and brown
arrows, respectively) are observed among the neoplastic glandular
cells (left lower). No POU2F3-positive tuft cells are noted in the
invasive carcinoma portion (right upper) [original magnification,
x40, x400 (inset)]. H-PGDS, haematopoietic prostaglandin D
synthase; IPMN, intraductal papillary mucinous neoplasm; POU2F3,
POU domain class 2 transcription factor 3. |
POU2F3-positive tuft cells were observed among the
neoplastic glandular cells in the lesions of IPMN with low- and
high-grade dysplasia (IPMN without invasive carcinoma) (Fig. 1B, C) and in the non-invasive regions of IMPN
associated with invasive carcinoma (Fig. 1D). The median number of
POU2F3-positive cells present in IPMN without invasive carcinoma
and in the non-invasive regions of IMPN associated with invasive
carcinoma was 12 cells/5-high power fields (range, 0-96 cells).
There was no significant difference in POU2F3-positive tuft cells
between IPMN without invasive carcinoma (median, 10 cells; range,
2-41 cells) and non-invasive regions of IPMN associated with
invasive carcinoma (median, 12.5; range, 0-96 cells) (P=0.085)
(Fig. 2A). The median ratio of
(POU2F3+/H-PGDS+)/[(POU2F3+/H-PGDS+)
+ (POU2F3+/H-PGDS-)] was 20.0% (range,
0-58.8%) in IPMN without invasive carcinoma and in the non-invasive
regions of IMPN associated with invasive carcinoma. There was no
significant difference in this ratio between IPMN without invasive
carcinoma (median, 32.4%; range, 0-58.8%) and non-invasive regions
of IPMN associated with invasive carcinoma (median, 7.3%; range,
0-53.8%) (P=0.190) (Fig. 2B).
In the invasive carcinoma regions of IPMN associated
with invasive carcinoma, few POU2F3-positive cells were observed
(median, 0 cells; range, 0-8 cells/5-high power fields) (Fig. 1D). There was a significant
difference in the number of POU2F3-positive tuft cells between the
non-invasive and invasive regions in IPMN associated with invasive
carcinoma (P=0.0180) (Fig. 2C).
The median ratio of
(POU2F3+/H-PGDS+)/[(POU2F3+/H-PGDS+)
+ (POU2F3+/H-PGDS-)] in the invasive regions
of IPMN associated with invasive carcinoma was 0% (range, 0-37.5%).
The ratio was significantly different between the non-invasive and
invasive regions in patients with IPMN associated with invasive
carcinoma (P=0.0277) (Fig.
2D).
In addition, the number of tuft cells were not
significantly different depending on the tumour location and the
clinical histories (such as comorbidities and smoking history).
Discussion
This study demonstrated that POU2F3-positive tuft
cells were present in human IPMN and that 20.0% of POU2F3-positive
cells in IPMN without invasive carcinoma and in non-invasive
regions of IPMN associated invasive carcinoma expressed H-PGDS.
Moreover, POU2F3-positive tuft cells and the ratio of H-PGDS
expression in POU2F3-positive tuft cells were significantly lower
in the invasive regions than in the non-invasive regions of
IPMN-associated invasive carcinoma.
Tuft cells play important roles in bacterial and
parasitic infections of the gastrointestinal and respiratory tracts
as chemosensory cells express taste receptors by producing various
types of physiologically active substances (6). Recent studies have demonstrated the
significance of tuft cells in tumourigenesis of some organs,
including gastric cancer (17-19)
and PDAC (7-9).
In pancreatic carcinogenesis, POU2F3-positive tuft cells emerge in
ADM, a possible precursor of PanIN, but not in normal acini in both
the human and mouse pancreas (7,8). ADM
is thought to be the trans-differentiation or de-differentiation of
pancreatic acinar cells after injury, and the possible role of tuft
cells in ADM lesions is to facilitate tissue repair from the injury
(6,20). Damaged acinar cells form ADM, in
which some of cells within ADM lesions are speculated to
differentiate into tuft cells in response to tissue injury, and the
alternative mechanism of presence of tuft cells, such as de
novo development from acinar cells, has not been considered
(20). These tuft cells within ADM
could facilitate tissue repair (20). Tuft cells are present in PanIN, a
possible precursor lesion of PDAC, and their levels are
significantly higher in low-grade PanIN than in high-grade PanIN in
the human pancreas (8), as well as
in the mouse pancreas using KrasG12D transgenic
models (7). Tuft cells present in
PanIN lesions have been speculated to suppress tumour progression
by producing PGD2 in a mouse model (7). Moreover, tuft cells have also been
paid attention in their oncogenic roles, because carcinomas with
tuft cell-like gene signatures, including POU2F3, namely ‘tuft
cell-like carcinoma’ has been reported (21). Small cell carcinomas of the lung
are the first to show tuft cell-like signatures, and it has been
demonstrated that thymic squamous cell carcinomas and a proportion
of other extra-thoracic carcinomas, such as breast and uterine
cervical carcinomas, show these signatures (21). Tuft cell-like gene signatures shows
oncogenic roles, because these signatures have important roles in
carcinogenesis of these malignant neoplasms (21). In contrast, tuft cells may have
suppressive roles in tumourigenesis of PDAC and IPMN via production
of PGD2 (7). Moreover,
in gastric tumourigenesis, tuft cells are present in dysplastic
lesions, but rarely present in the adenocarcinoma (19), as the same line of the results of
PanIN, PDAC (7), and IPMN. In
pancreatic and gastric tumourigenesis, tuft cells show
tumour-suppressive roles (7,19),
although PGD2 plays important roles in
tumour-suppressive function in PanIN, PDAC, as well as IPMN
(7), but its roles in gastric
tumourigenesis remains unresolved (19). These key findings appear to be
dual-faceted of tuft cells, having both tumour-promoting and
tumour-suppressive roles (22).
Although the reason of these different roles of tuft cells remains
controversial, it might depend on the organ or molecular context
roles of tuft cells and tumour microenvironment might influence the
function of tuft cells (22). Tuft
cells are present both in the normal respiratory and
gastrointestinal tracts, and the thymus (6,23),
and functions of tuft cells may be different among organs (23). These original function of tuft
cells depending on the organs and their tumour microenvironment
might influence the oncogenic or tumour-suppressive function of
tuft cells (22,23). Additional studies are needed to
clarify the roles of tuft cells in various types of tumours.
IPMN is the second common precursor lesion of
invasive carcinoma of the pancreas (3). Although previous studies have
revealed the significance of tuft cells in tumourigenesis from
PanIN to PDAC (7,8), only one study has addressed the
presence of tuft cells in IPMN (10). In that report, tuft cells were
present in IPMN and were rarely observed in invasive carcinoma
components in a mouse model, although doublecortin-like kinase1
(DCLK1) was used as an immunohistochemical marker for detecting
tuft cells (10). The results of
the present study showed that IPMN with low- and high-grade
dysplasia and non-invasive regions of IPMN associated with invasive
carcinoma had POU2F3-positive tuft cells, and the number of tuft
cells between these lesions was not significantly different. These
results are consistent with those of a previous study (10), although the immunohistochemical
markers used to detect tuft cells were different. POU2F3 was used
as a tuft cell marker in the present study because it is considered
a more specific marker for human tuft cells owing to the nature of
the master regulator of this type of cell (6,12,24).
PGs are lipid mediators involved in inflammation and
smooth muscle and vascular dilatation in various types of tissues
(25). PGD2 is a PG
that plays a pivotal role in inflammation and tissue injury
(13,25). PGD2 is synthesised from
two different types of PGDS: H-PGDS and lipocalin-type PGDS
(25). H-PGDS is expressed in
certain types of immune cells, including macrophages, mast cells,
and a subset of T lymphocytes (13,26).
Immunohistochemical staining is a useful method for demonstrating
PGD2 production (7,11,13,14).
Our previous study clearly demonstrated that tuft cells expressing
H-PGDS were present in Warthin's tumour, the second most common
benign salivary gland tumour, and its expression might be related
to tissue injury within the tumour (10). The present study clearly
demonstrated that 20.0% of POU2F3-positive tuft cells present in
IPMN without invasive carcinoma and the non-invasive regions of
IPMN associated with invasive carcinoma expressed H-PGDS and
POU2F3-positive tuft cells and that the ratio of POU2F3-positive
tuft cells expressing H-PGDS were significantly lower in the
invasive portions compared with the non-invasive regions in IPMN
associated with invasive carcinoma for the first time. It has been
recognized that PGD2 secreted from tuft cells in PanIN
lesions shows tumour-suppressive functions from PanIN to PDAC, and
these tuft cells are thought to be differentiated from PanIN
lesions, however, carcinoma cells in PDAC have no potential to
differentiation into tuft cells and production of PGD2,
thus, tuft cells are hardly present in PDAC lesions (7,27).
The results of the present study were fundamentally the same line
of those of PanIN and PDAC, because tuft cells were hardly present
in the invasive carcinoma component of IPMN, but present in
non-invasive regions. Non-invasive IPMN could have potential to
differentiate into tuft cells, which play possible
tumour-suppressive roles via production of PGD2, but
most of invasive carcinoma cells of IPMN might lack potential to
differentiate into tuft cells. These results suggest that
POU2F3-positive tuft cells have roles in progression to carcinoma
in IPMN, similar to tuft cell function in PanIN and PDAC (7,8). No
detailed molecular mechanism regarding the lack of potential to
differentiate to tuft cells in tumourigenesis of PDAC, as well as
invasive carcinoma component of IPMN, has been elucidated (7,27),
therefore, further studies are needed to clarify this issue. In the
present study, we did not perform a statistical analysis to compare
the number of POU2F3-positive tuft cells and the ratio of H-PGDS
expression between IPMN with low- and high-grade dysplasia because
only two patients with IPMN with high-grade dysplasia were
included. Therefore, additional studies with larger cohorts are
required to clarify the differences in tuft cells between IPMN with
low- and high-grade dysplasia. Moreover, although the presence of
tuft cells in the non-neoplastic human pancreatic duct has been
recognised (8), the present study
showed that more than half of POU2F3-positive tuft cells present in
the non-neoplastic pancreatic duct expressed H-PGDS. Although the
functions of these cells remain unclear, they are thought to
modulate immune reactions or tissue repair. Additionally, one of
the interesting findings of the present study was the presence of
POU2F3-positive tuft cells in the invasive carcinoma region of IPMN
associated with invasive carcinoma. It has been reported that
POU2F3-positive tuft cells were not present in PDAC in a mouse
model (7); however, our
provisional study revealed that a few POU2F3-positive tuft cells
were noted in PDAC in some cases (unpublished data), which is
similar to the results of the present study. Thus, POU2F3-positive
tuft cells may be present in invasive pancreatic carcinomas (both
PDAC and IPMN associated with invasive carcinoma); thus, the
clinicopathological features of POU2F3-positive tuft cells in
invasive pancreatic carcinomas must be clarified.
This study has some limitations. First, this study
included relatively few patients with pancreatic IPMN, especially
those with IPMN with high-grade dysplasia, which could have led to
a selection bias. Moreover, the number of tuft cells and the ratio
of tuft cells expressing H-PGDS showed relative variations among
the tumours. The possibility that tumours locations or clinical
histories may influence the number of tuft cells cannot be ruled
out, because these factors were not controlled in the present
study. Although the number of tuft cells were not significantly
different depending on the tumour location and the clinical
histories, the possibility that these factors may influence the
degree or extent of obstructive pancreatitis and tissue repair,
leading to the changes of the number of tuft cells, cannot be
excluded. Second, although IPMN are subclassified by
immunohistochemical analyses for mucin into gastric, intestinal,
and pancreatobiliary types (4),
this subclassification was not performed in the present study. The
possibility of differences in the number of tuft cells and the
ratio of tuft cells expressing H-PGDS among these
subclassifications cannot be ruled out. Validation studies with
larger numbers of patients with IPMN are required to overcome
statistical bias. Third, the present study showed the presence of
POU2F3-positive tuft cells expressing H-PGDS in IPMN; however, the
function of PGD2 production in IPMN and the differences
between H-PGDS-positive and H-PGDS-negative tuft cells remain
unclear. Further analyses using mouse models are required to
elucidate the function of tuft cells in IPMN, leading to the
elucidation of IPMN. Fourth, POU2F3 was used as a human tuft cell
marker in the present study, and immunohistochemical analysis using
other markers, including DCLK-1, transient receptor potential
melastatin 5 (TRPM5), and cyclooxygenase 1 (COX1), were not
performed. Although these markers have been used as a marker for
tuft cells, DCLK-1 is specific for mouse tuft cells, but not for
human ones (6). TRPM5 is also
expressed in pancreatic beta cells and taste buds (28), and COX1 expression is not specific
for tuft cells (29). Moreover, as
described-above, POU2F3 is a master regulator of tuft cell
identity, thus, we used it as a human tuft cell marker in the
present study (8). Finally, we did
not perform the experiment using animal model, which might provide
new information regarding the function of tuft cells in IPMN,
because the aim of the present study was to show the roles of tuft
cells in human IPMN tissues.
In conclusion, this study showed that
POU2F3-positive tuft cells expressing H-PGDS were present in human
IPMN and were hardly detected in the invasive regions of IPMN
associated with invasive carcinoma. POU2F3-positive tuft cells
producing PGD2 might play a role in tumourigenesis in
IPMN. Further analyses are required to clarify the function of tuft
cells in IPMN, resulting in the resolution of the pathogenesis of
IPMN.
Acknowledgements
The authors express their gratitude to Ms. Shizuka
Ono, Mr. Yusuke Ohnishi and Mr. Naoto Kohno (Department of
Pathology, Osaka Medical and Pharmaceutical University) for their
technical assistance with this study.
Funding
Funding: No funding was received.
Availability of data and materials
The data generated in the present study may be
requested from the corresponding author.
Authors' contributions
KN and MI conceived and designed the study. KN, MI,
and KH analysed the histological and immunohistochemical staining.
KN, MI, KH, KT, JA, AT, MA, YM, KF, YH and SWL analysed the data.
KN and MI performed the statistical analyses. KN and MI wrote the
manuscript, and prepared the figures and tables. KN and MI confirm
the authenticity of all the raw data. All authors read and approved
the final manuscript.
Ethics approval and consent to
participate
This retrospective, single-institution study was
conducted in accordance with the tenets of The Declaration of
Helsinki. The study protocol was approved by the Institutional
Review Board of Osaka Medical and Pharmaceutical University
Hospital (approval no. 2023-198). All data were anonymised.
Informed consent was obtained from the patients using the opt-out
methodology because of the retrospective study design, as medical
records and archived samples were used with no risk to the
participants. Moreover, the present study did not include
minors.
Patient consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing
interests.
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