Neoadjuvant Radiochemotherapy in Esophageal Adenocarcinoma Is Associated with a Dense IgG4 Plasma Cell Response
Danisha Allen, Shaolei Lu, Lelia Noble, Jacqueline Fanion, Murray B Resnick, Evgeny Yakirevich. Rhode Island Hospital and the Alpert Medical School of Brown University, Providence, RI
Background: Lymphoplasmacytic infiltrates, the primary immune component infiltrating solid tumors, are considered to be a manifestation of the host anti-tumor response. Recently we have noticed the presence of a dense plasma cell infiltrate in esophagectomy specimens of patients with esophageal adenocarcinoma who underwent neoadjuvant radiochemotherapy. The aim of this study was to quantify and further characterize the plasma cell infiltrates in esophageal adenocarcinomas with respect to IgG4 expression.
Design: Fifty consecutive esophagectomy specimens of esophageal adenocarcinoma were selected including 35 following neoadjuvant radiochemotherapy, and 15 with no previous history of radiochemotherapy (NT). The treatment response was evaluated as complete (CR), partial (PR), or no response (NR). Formalin-fixed paraffin embedded sections were stained for IgG4 and IgG by immunohistochemistry. Areas with the highest density of IgG4+ and IgG+ plasma cells were selected, the average of the three most cellular areas per high power field (hpf) were counted, and IgG4+ to IgG+ ratios were calculated.
Results: Of the 35 patients treated with neoadjuvant radiochemotherapy six had a complete response, 23 partial response and six no response. None of the patients had an IgG4-related sclerosing disease. The number of IgG4+ plasma cells varied between 0 and 297 per hpf; the number of IgG+ plasma cells ranged between 0 and 336 per hpf. The absolute number of IgG4+ plasma cells was increased in the area of the tumor bed in the CR group as compared to the PR, NR, and NT groups (114.5±55.3, 79.0±18.9, 23.7±8.2, and 35.6±11.9 per hpf, respectively). Furthermore, the ratio of IgG4+/IgG+ plasma cells was markedly elevated in the CR group and PR group as compared to the NR group (44%, 40%, and 18%, respectively). The CR group contained significantly more tumors with >50 IgG4+ plasma cells per hpf and >50% IgG4+/IgG+ ratio as opposed to PR and NR (50%, 39%, and 0%, respectively, p=0.05). At this point it is not clear whether the degree of the IgG4 response confers a survival advantage.
Conclusions: This is the first study to identify and characterize a dense IgG4 plasma cell infiltrate in esophageal adenocarcinoma following neoadjuvant radiochemotherapy. The association of elevated IgG4+ plasma cells with complete treatment response suggests that it may play a role in the neoadjuvant therapy related immune response.
Monday, March 4, 2013 1:00 PM
Poster Session II # 115, Monday Afternoon