IgG4 Expression Correlates with Poor Prognosis in Pancreatic Adenocarcinoma

Budd, W; Mukherjee, Abhik; Lobo, DR; Zaitoun, AM

Abstract

Purpose of the study: IgG4, a member of the immunoglobulin family, has been implicated in the pathobiology of inflammatory disease (including autoimmune pancreatitis) and cancers. Its role in pancreatic cancers however remains to be elucidated. This study aimed to examine the role of IgG4 in pancreatic cancer, in both tumoural and inflammatory components.
Methods: The expression of IgG4 in pancreatic adenocarcinomas was studied by immuno-histochemical analysis of a tissue microarray (n=142) and analysed for clinicopathological correlations. The tumour inflammatory infiltrate, IgG4 positive lymphocytes (LCA stained) and plasma cells (CD138 stained) were investigated to understand their role in pancreatic malignancies.
Summary of results: Pancreatic tumour cells showed three positive patterns of staining: 47 (33%) golgi, 26 (18.3%) nuclear and 100 (70.4%) cytoplasmic. Significant positive correlations for tumoural IgG4 were observed with pancreatic cancer stage, grade, perineural invasion and recurrence (p < 0.05). IgG4 positive lymphocytic infiltrate was seen in 98 (69%) cases and presence at the tumour edge correlated with perineural invasion (p= 0.03). 80 (56%) cases exhibited an IgG4 positive plasma cell infiltrate which correlated with T stage (p=0.02) and vascular invasion (p= 0.04). Tumours with both strong golgi expression in tumour cells and high IgG4 positive lymphocytic infiltrate showed positive correlation with recurrence (p=0.01).
Conclusions: Overall, this study shows that IgG4, expressed in pancreatic tumour cells and its associated lymphoplasmacytic infiltrate, has significant correlations with poor prognostic features. Further exploration of the immunological milieu of pancreatic tumours will validate the functional significance of IgG4 associated immune networks in pancreatic malignancies.

• Conference Name: Leeds Pathology 2019. 12th Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland, 2–4 July 2019
• Conference Location: Leeds, England
• Start Date: Jul 2, 2019
• End Date: Jul 4, 2019
• Acceptance Date: Apr 25, 2019
• Online Publication Date: Sep 16, 2019
• Publication Date: Sep 16, 2019
• Deposit Date: Nov 14, 2019
• Publicly Available Date: Feb 16, 2021
• Publisher: Wiley
• Volume: 249
• Pages: S1-S59
• Series ISSN: 1096-9896
• Book Title: Supplement: Leeds Pathology 2019. 12th Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland, 2–4 July 2019
• DOI: https://doi.org/10.1002/path.5345
• Public URL: https://nottingham-repository.worktribe.com/output/3279889
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1002/path.5345