Usefulness of endoscopic biopsy using FOXP3+ Treg up-regulation in the duodenal papilla in the differential diagnosis between autoimmune pancreatitis and pancreatic cancer.
OBJECTIVE
Expression of the forkhead/winged helix family of transcription factor P3+ regulatory T cells (FOXP3(+) Treg), a master gene of regulatory T cells (Treg) is observed in patients with autoimmune pancreatitis (AIP). We investigated the usefulness of detection of FOXP3(+) Treg in the main duodenal papilla for differential diagnosis between AIP and pancreatic cancer (Pca).


METHODS
Firstly, we determined the cut-off value of FOXP3 expression in duodenal papilla taken from the patients with AIP (n = 22) and chronic pancreatitis (n = 21). Data from 32 patients with AIP and 30 patients with Pca who had undergone endoscopic biopsy were then studied. The numbers of FOXP3(+) Treg-positive lymphocytes and IgG4-positive plasma cells per high-power field (HPF) were counted in all the histopathological specimens.


RESULTS
The areas under the receiver-operating characteristic (AUROC) curves for FOXP3(+) and IgG4 expression were 0.934 and 0.953, respectively. Cut-off values calculated based on AUROC data were 14/HPF in FOXP3 and 10/HPF in IgG4. Seropositivity for IgG4 was observed in 22 out of the 31 patients with AIP (sensitivity 71.0%, specificity 84.6%, accuracy 75.0%). Significant infiltration of the major duodenal papilla by FOXP3(+) lymphocytes (≥ 14/HPF) was recognized in 18 of the 32 patients with AIP (sensitivity 56.3%, specificity 100%, accuracy 77.4%). Significant infiltration of the major duodenal papilla by IgG4-positive plasma cells (≥ 10/HPF) was recognized in 27 of the 32 patients with AIP (sensitivity 84.4%, specificity 80.0%, accuracy 82.3%).


CONCLUSIONS
Observation of FOXP3(+) cells in the main duodenal papilla may be useful in the differential diagnosis between AIP and Pca.
Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Fukuura 3-9, Kanazawa, Yokohama, 236-0004, Japan. kubotak@yokohama-cu.ac.jp
Kensuke
K
Kubota
Shingo
S
Kato
Seitaro
S
Watanabe
Koji
K
Fujita
Masato
M
Yoneda
Hirokazu
H
Takahashi
Masahiko
M
Inamori
Takeshi
T
Shimamura
Hiroyuki
H
Kirikoshi
Noritoshi
N
Kobayashi
Satoru
S
Saito
Kantaro
K
Hisatomi
Nobuyuki
N
Matsuhashi
Atsushi
A
Nakajima
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015551:Autoimmunity / Q000502:physiology; D001706:Biopsy / Q000379:methods; D002760:Cholangiopancreatography, Endoscopic Retrograde / Q000379:methods*; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010183:Pancreatic Ducts / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010195:Pancreatitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D012372:ROC Curve; D012189:Retrospective Studies; D015854:Up-Regulation; D055815:Young Adult
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors