Interleukin-33 overexpression reflects less aggressive tumour features in large-duct type cholangiocarcinomas.

Abstract

AIMS:

The aim of the present study was to elucidate the clinicopathological significance of interleukin (IL)-6 and IL-33 expression in intrahepatic cholangiocarcinomas (iCCAs) and perihilar cholangiocarcinomas (pCCAs).

METHODS AND RESULTS:

IL-6 and IL-33 mRNA expression levels were examined in iCCAs (n = 55) and pCCAs (n = 32) by the use of quantitative real-time polymerase chain reaction and a highly sensitive in-situ hybridisation protocol (RNAscope), and expression levels were correlated with clinicopathological features. According to a recently proposed classification scheme, iCCAs 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 iCCAs and pCCAs than in small-duct iCCAs, 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 CD31-positive endothelial cells. With the average expression level as a cut-off point, cases were classified as IL-6high and IL-6low or IL-33high and IL-33low . In the combined cohort of large-duct iCCAs and pCCAs, IL-6high and IL-6low cholangiocarcinomas shared many features, whereas IL-33high cases had less aggressive characteristics than IL-33low 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-33high cases than in IL-33low 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-33high cholangiocarcinomas may represent a unique, less aggressive carcinogenetic process of the large bile ducts.

• Authors: Ryuichiro Sawada, Yuna Ku, Masayuki Akita, Kyoko Otani, Kohei Fujikura, Tomoo Itoh, Tetsuo Ajiki, Takumi Fukumoto, Yoshihiro Kakeji, Yoh Zen
• Journal: Histopathology (Histopathology) Vol. 73 Issue 2 Pg. 259-272 (Aug 2018) ISSN: 1365-2559 [Electronic] England
• PMID: 29675965 (Publication Type: Journal Article)
• Copyright: © 2018 John Wiley & Sons Ltd.

Chemical References

• Biomarkers, Tumor
• IL33 protein, human
• IL6 protein, human
• Interleukin-33
• Interleukin-6

Topics

• Adult
• Aged
• Bile Duct Neoplasms (metabolism, mortality, pathology)
• Bile Ducts, Intrahepatic (pathology)
• Biomarkers, Tumor (analysis)
• Cholangiocarcinoma (metabolism, mortality, pathology)
• Disease-Free Survival
• Female
• Humans
• Interleukin-33 (analysis, biosynthesis)
• Interleukin-6 (analysis, biosynthesis)
• Kaplan-Meier Estimate
• Klatskin Tumor (metabolism, mortality, pathology)
• Male
• Middle Aged