IgG4 Reaction in Biliary Intraepithelial Neoplasia and Cholangiocarcinoma Arising from Sclerosing Cholangitis
Kenichi Harada, Yasunori Sato, Hirohide Sato, Hiroko Ikeda, Yasuni Nakanuma. Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa, Japan; Kanazawa University Hospital, Kanazawa, Ishikawa, Japan
Background: The IgG4 reaction, consisting of marked IgG4-positive cell infiltration, was found in cholangiocarcinoma as well as IgG4-related sclerosing cholangitis (IgG4-SC). We have reported that IgG4 reaction in cholangiocarcinoma is a localized cancer-associated immune reaction to evade immune surveillance in an IL-10-related regulatory cytokine milieu. In this study, we examined IgG4 reaction in biliary intraepithelial neoplasia (BilIN) and cholangiocarcinoma arising from sclerosing cholangitis to clarify the significance of IgG4 reaction in the carcinogenesis of cholangiocarcinoma.
Design: Partial hepatectomy and explanted liver specimens were obtained from 6 patients with primary sclerosing cholangitis (PSC) (2 patients associated with overt cholangiocarcinoma) and 7 IgG4-SC. Using paraffin sections, immunohistochemistry for IgG4 and S100P (a phenotypic marker of BilIN and cholangiocarcinoma) was performed.
Results: IgG4-positive cells were scattered 5-23/hpf in S100P-positive BilIN as well as cholangiocarcinoma in 2 cases of PSC with cholangiocarcinoma, but there were none or few in those without cholangiocarcinoma irrespective of accompanying S100P-positive BilIN or not. In IgG4-SC, numerous IgG4-positive cells were found in all cases. Moreover, S100P-positive BilIN was found regionally in 2 of 6 cases, but there was no difference in IgG4 reaction between BilIN and non-BilIN regions.
Conclusions: In PSC cases with cholangiocarcinoma, IgG4 reaction was seen in BilIN as well as cholangiocarcinoma, but not in PSC without cholangiocarcinoma, irrespective of the presence of BilIN or not. These findings suggest that IgG4-related tumor immune reaction is associated with the development from BilIN to cholangiocarcinoma in PSC, rather than the histogenesis of BilIN. In addition to PSC, IgG4-SC, in which the IL-10-related regulatory cytokine milieu is associated with the pathogenesis, possessed S100P-positive BilIN lesions, suggesting that IgG4-SC is also a possible preceding disease of cholangiocarcinoma.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 154, Tuesday Afternoon