Helicobacter pylori-related diffuse large B-cell lymphoma of the stomach: a distinct entity with lower aggressiveness and higher chemosensitivity

Abstract

We recently showed that Helicobacter pylori (HP)-positive gastric 'pure' diffuse large B-cell lymphoma (DLBCL) may respond to HP eradication therapy. However, whether these HP-related 'pure' DLBCL of the stomach may differ fundamentally from those unrelated to HP remains unclear. In this study, we compared the clinicopathologic features of these two groups of patients who had been uniformly treated by conventional chemotherapy. Forty-six patients were designated HP-positive and 49 were HP-negative by conventional criteria. HP-positive patients had a lower International Prognostic Index score (0-1, 65% vs 43%, P=0.029), a lower clinical stage (I-IIE1, 70% vs 39%, P=0.003), a better tumor response to chemotherapy (complete pathologic response, 76% vs 47%, P=0.004) and significantly superior 5-year event-free survival (EFS) (71.7% vs 31.8%, P<0.001) and overall survival (OS) (76.1% vs 39.8%, P<0.001). To draw a closer biologic link with HP, HP-positive tumors were further examined for CagA expression in lymphoma cells. Compared with CagA-negative cases (n=16), CagA-positive cases (n=27) were associated with high phosphorylated SHP-2 expression (P=0.016), and even better 5-year EFS (85.2% vs 46.3%, P=0.002) and OS (88.9% vs 52.9%, P=0.003). HP-related gastric 'pure' DLBCL may be a distinct tumor entity, which is less aggressive, and responds better to conventional chemotherapy.

Figure 1

Association of HP status with clinical outcome in gastric ‘pure' DLBCL. (a) Relationship of HP status to EFS. (b) Relationship of HP status to OS.

Figure 2

Examples of immunohistochemical analysis of CagA protein on tumor cells of gastric ‘pure' DLBCL. (a) Diffuse large cells infiltrating the mucosa are observable on histopathologic examination (hematoxylin–eosin (H&E), × 400) (arrow, HP). (b) Diffuse large cells infiltrating the submucosa are observable on histopathologic examination of an HP-positive case (H&E, × 400). (c) The same HP-positive case (b) shows CagA expression in the tumor cells (right bottom inset, × 1000). (d) HP-positive case shows CagA expression in the tumor cells of gastric mucosa. (e) HP-positive case shows CagA expression in the tumor cells of gastric submucosa (right bottom inset, × 1000). (f) Double stains: tumor cells with CagA nuclear staining (brown color) are also CD20-positive (red color) (right bottom inset, × 1000).

Figure 3

Association of CagA expression with clinical outcome in HP-positive gastric ‘pure' DLBCL. (a) Relationship of CagA status to EFS. (b) Relationship of CagA status to OS.