**Abstract**

Early stage gastric diffuse large B-cell lymphomas (DLBCLs) with histological features of mucosa-associated lymphoid tissue (MALT) origin (DLBCL[MALT]) are also closely related to *Helicobacter pylori* (*Hp*) infection, apart from the classical gastric MALT lymphoma, and are cured by *Hp* eradication therapy (HPE). Whether some gastric "pure" DLBCLs (without histological features of MALT) are also *Hp*-related is clinically very important, since this subtype of gastric lymphoma is relatively common in the population and is still universally treated with intensive systemic chemotherapy. A large proportion of early stage gastric "pure" DLBCL can achieve long-term complete remission after HPE. However, the precise mechanisms of *Hp*-dependent (with complete regression of tumors after HPE) lymphomagenesis of gastric "pure" DLBCL, DLBCL(MALT), and MALT lymphoma remain uncertain. In the classical conception, gastric MALT lymphoma is indirectly caused by *Hp* through T-cell stimulation, with the aid of costimulatory molecules. To explore the direct interactions between *Hp* and lymphoma B-cells of *Hp*-dependent gastric MALT lymphoma, DLBCL(MALT), and "pure" DLBCLs, we assessed the participation of *Hp*-encoded cytotoxin-associated gene A (CagA) in the lymphomagenesis of these tumors. We discovered that CagA oncogenic protein and its regulated signaling molecules including phospho-Src homology-2 domaincontaining phosphatase (p-SHP-2) and phospho-extracellular signal-regulated kinase (p-ERK) correlated significantly with *Hp*-dependence of gastric MALT lymphoma. This finding supports previous observations that the CagA protein of *Hp* can be translocated into B-cell lymphoma cells, thereby leading to survival signals. Furthermore, we demonstrated that *Hp*-positive and CagA-expressing gastric "pure" DLBCLs behave in a less biologically aggressive manner, and have better clinical outcomes; this is a distinguishing entity, and its cell origin may include germinal center B cells. In addition, we found that the expression of CagA, p-SHP-2, and p-ERK correlated significantly with the *Hp*-dependence of gastric DLBCL(MALT) and "pure" DLBCL. These findings indicate that the spectrum of *Hp*-related gastric lymphomas including MALT lymphoma, DLBCL(MALT), and "pure" DLBCL, is much wider than was previously thought. Further explorations of the spectrum, lymphomagenesis, and therapeutics of *Hp*-related gastric lymphoma are warranted.

**Keywords:** *Helicobacter pylori*, MALT, DLBCL, Stomach, CagA
