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

Abstract

We previously reported that early-stage gastric diffuse large B-cell lymphomas (DLBCLs), including DLBCLs with mucosa-associated lymphoid tissue (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 cytotoxin-associated gene A (CagA) and CagA-signaling molecules (phospho-Src homology-2 domain-containing phosphatase [p-SHP2] and phospho-extracellular signal-regulated kinase [p-ERK]) is associated with 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 of 42 DLBCL (MALT) cases (47.6%) and in 13 of 21 "pure" DLBCL cases (61.9%). CagA expression was higher in HP-dependent tumors than in HP-independent tumors (74.3% [26 of 35] vs 25.0% [7 of 28]). Patients with CagA expression responded to HPE quicker than those without expression (median time to complete remission, 4.0 months vs 5.0 months). The expression of CagA was closely associated with p-SHP-2 and p-ERK expression. Combined CagA, p-SHP-2, and p-ERK expression showed an increased positive predictive value (81.8% vs 75.9%) and an increased specificity (84.0% vs 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.

• Authors: 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, Ann-Lii Cheng
• Journal: Blood (Blood) Vol. 129 Issue 2 Pg. 188-198 (01 12 2017) ISSN: 1528-0020 [Electronic] United States
• PMID: 27864293 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 by The American Society of Hematology.

Chemical References

• Anti-Bacterial Agents
• Antigens, Bacterial
• Bacterial Proteins
• cagA protein, Helicobacter pylori
• Extracellular Signal-Regulated MAP Kinases
• Protein Tyrosine Phosphatase, Non-Receptor Type 11

Topics

• Adult
• Aged
• Aged, 80 and over
• Anti-Bacterial Agents (therapeutic use)
• Antigens, Bacterial (biosynthesis)
• Bacterial Proteins (biosynthesis)
• Extracellular Signal-Regulated MAP Kinases (biosynthesis)
• Female
• Helicobacter Infections (complications, drug therapy, metabolism)
• Humans
• Immunohistochemistry
• Lymphoma, Large B-Cell, Diffuse (microbiology)
• Male
• Microscopy, Confocal
• Middle Aged
• Protein Tyrosine Phosphatase, Non-Receptor Type 11 (biosynthesis)
• Stomach Neoplasms (microbiology, pathology)
• Young Adult