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Interleukin‐33 overexpression reflects less aggressive tumour features in large‐duct type cholangiocarcinomas
Author(s) -
Sawada Ryuichiro,
Ku Yuna,
Akita Masayuki,
Otani Kyoko,
Fujikura Kohei,
Itoh Tomoo,
Ajiki Tetsuo,
Fukumoto Takumi,
Kakeji Yoshihiro,
Zen Yoh
Publication year - 2018
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13633
Subject(s) - immunostaining , duct (anatomy) , pathology , messenger rna , biology , immunohistochemistry , gastroenterology , medicine , gene , biochemistry
Aims The aim of the present study was to elucidate the clinicopathological significance of interleukin ( IL )‐6 and IL ‐33 expression in intrahepatic cholangiocarcinomas ( iCCA s) and perihilar cholangiocarcinomas ( pCCA s). Methods and results IL ‐6 and IL ‐33 mRNA expression levels were examined in iCCA s ( n = 55) and pCCA s ( n = 32) by the use of quantitative real‐time polymerase chain reaction and a highly sensitive in‐situ hybridisation protocol ( RNA scope), and expression levels were correlated with clinicopathological features. According to a recently proposed classification scheme, iCCA s were separated into small‐duct ( n = 33) and large‐duct ( n = 22) types. IL ‐6 and IL ‐33 expression levels were higher in large‐duct iCCA s and pCCA s than in small‐duct iCCA s, and there was a positive correlation between the expression levels of these cytokines. Double in‐situ hybridisation/immunostaining showed that IL ‐6 mRNA was expressed in actin‐positive (myo)fibroblasts, whereas IL ‐33 mRNA was mainly produced by CD 31‐positive endothelial cells. With the average expression level as a cut‐off point, cases were classified as IL ‐6 high and IL ‐6 low or IL ‐33 high and IL ‐33 low . In the combined cohort of large‐duct iCCA s and pCCA s, IL ‐6 high and IL ‐6 low cholangiocarcinomas shared many features, whereas IL ‐33 high cases had less aggressive characteristics than IL ‐33 low cases, as shown by lower tumour marker concentrations, smaller tumour sizes, less common vascular invasion, lower pT stages, and higher lymphocyte/monocyte ratios in blood. KRAS mutations were slightly less common in IL ‐33 high cases than in IL ‐33 low cases (9% versus 29%; P = 0.061). The strong expression of IL ‐33 in tissue appeared to be an independent favourable prognostic factor. Conclusions IL ‐33 high cholangiocarcinomas may represent a unique, less aggressive carcinogenetic process of the large bile ducts.