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Expressions of the CagA protein and CagA-signaling molecules predict H. pylori-dependence of early-stage gastric DLBCL

Sung-Hsin Kuo, Li-Tzong Chen, Chung-Wu Lin, Kun-Huei Yeh, Chia-Tung Shun, Yi-Shin Tzeng, Jyh-Ming Liou, Ming-shiang Wu, Ping-Ning Hsu and Ann-Lii Cheng

Key points

  • Expression of CagA and CagA-signaling molecules p-SHP2 and p-ERK is associated with HP-dependence of gastric diffuse large B-cell lymphoma

  • CagA is associated with the direct lymphomagenic effect of HP on B cells of HP-dependent gastric diffuse large B-cell lymphoma

Abstract

We previously reported that early-stage gastric diffuse large B-cell lymphomas (DLBCLs), including DLBCLs with (DLBCL[MALT]) and without ('pure' DLBCL) the features of MALT lymphomas, can achieve long-term complete remission after frontline Helicobacter pylori (HP) eradication (HPE). We recently reported that expression of CagA and CagA-signaling molecules (p-SHP2 and p-ERK) is associated with the HP-dependence of gastric MALT lymphoma. However, the significance of CagA and CagA-signaling molecules in gastric DLBCL remains unexplored. The association between expression of CagA, p-SHP-2, and p-ERK in malignant B-cells and tumor response to HPE was evaluated in 63 patients with stage IE/IIE1 HP-positive gastric DLBCL who received HPE as frontline treatment. We detected CagA expression in 20 (47.6%) of 42 DLBCL(MALT) cases and in 13 (61.9%) of 21 'pure' DLBCL cases. CagA expression was higher in HP-dependent tumors than in HP-independent tumors (74.3% [26/35] versus 25.0% [7/28], P < .001). Patients with CagA expression responded to HPE quicker than those without expression (median time to complete remission, 4.0 months versus 5.0 months, P = .05). The expression of CagA was closely associated with p-SHP-2 (P < .001) and p-ERK (P = .002) expression. Combined CagA, p-SHP-2, and p-ERK expression showed an increased positive predictive value (81.8% versus 75.9%) and an increased specificity (84.0% versus 75.0%) for HP-dependence compared with CagA expression alone. Our results indicated that CagA and its signaling molecules can be detected in the malignant B-cells of gastric DLBCL, and the expression of these molecules is clinically and biologically associated with HP-dependence.

  • Submitted April 28, 2016.
  • Accepted November 9, 2016.