Prognostic Significance of IgG4+ Plasma Cell Infiltrates Following Neoadjuvant Chemoradiation Therapy for Esophageal Adenocarcinoma

Publication date: Available online 28 June 2017
Source:Human Pathology
Author(s): Evgeny Yakirevich, Shaolei Lu, Danisha Allen, Shamlal Mangray, Jacqueline R Fanion, Kara A Lombardo, Howard Safran, Murray B Resnick
Lymphoplasmacytic infiltrates in esophageal adenocarcinoma (EAC) tissue following chemoradiotherapy (CRT) reflect alterations in the tumor immunoenvironment. The presence and role of plasma cells in this process are poorly understood. Our aim was to characterize the IgG4+ plasma cell population in EAC following CRT. Seventy-one esophagectomy specimens post CRT were compared to a surgery only group of 31 EACs. The distribution, density, and ratio of IgG4+ and IgG+ plasma cells were evaluated by immunohistochemistry and correlated with clinicopathologic features, treatment response, and survival. In the CRT group the presence of higher numbers of IgG4+ (≥ median of 94/high power field) and IgG+ (≥ median of 225/high power field) plasma cells and increased IgG4+/IgG+ ratio(≥ median of 41%) within ulcers was associated with complete or near complete treatment response (P=.0077, P=.0503, and P=.0063, respectively). Lower tumor grade, smaller tumor size, and higher levels of IgG4+ plasma cells in posttherapy ulcers significantly correlated with better overall survival (OS), while pretherapy clinical stage, posttherapy pathologic stage, smaller tumor size and lower tumor grade were associated with longer recurrence free survival (RFS). Multivariate analysis revealed that both posttherapy pathologic stage and high IgG4+ plasma cells in ulcers were independent predictors of OS (P=.05 and P=.01), whereas only posttherapy pathologic stage was associated with RFS (P<.01). This is the first study describing a dense IgG4+ plasma cell infiltrate in EAC following CRT. The presence of increased IgG4+ plasma cells may be a novel reliable factor to predict prognosis of EAC patients following CRT.



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