IgG4 expression and IgG4/IgG ratio in the tumour invasion front predict long-term outcomes for patients with intrahepatic cholangiocarcinoma

Abstract

IgG4-positive plasma cells are reportedly increased in the tumour microenvironment, and a high number of these cells in tumours is a poor prognostic factor in several cancers. However, there are no reported analyses of IgG4 expression in intrahepatic cholangiocarcinoma (ICC). This study aimed to analyse the correlations between prognosis-related clinicopathological features of patients with ICC and IgG4 expression. We identified 37 ICC patients who underwent surgical resection between January 2010 and December 2020. The number of IgG-positive and IgG4-positive plasma cells in the tumour, invasion front, and stroma near the tumour was analysed by immunostaining. Furthermore, we examined the association of prognosis-related clinicopathological data with the number of IgG4-positive plasma cells and IgG4/IgG ratio in ICC patients. The IgG4-positive plasma cell percentages for the intra-tumour area, invasion front, and non-cancerous area (NCA) near the tumour were 91.9%, 56.8%, and 81.1%, respectively. IgG-positive plasma cells were observed in each region for all cases, except for NCA tissue in one case. A high IgG4 expression level and IgG4/IgG ratio in the invasion front were significantly associated with poor overall survival (OS) (log-rank test p=0.0438 and p=0.0338, respectively). Multivariate analysis for OS revealed that high IgG4 expression (p=0.0140), lymph node metastasis (p=0.0205), and positive surgical margin (p=0.0009) or a high IgG4/IgG ratio (p=0.0051), lymph node metastasis (p=0.0280), and positive surgical margin (p=0.0009) were independent poor prognostic factors. In conclusion, a high IgG4 expression level and IgG4/IgG ratio in the invasion front are independent poor prognostic factors for ICC. Targeted therapy for IgG4 may improve the prognosis for patients with ICC.