Abstract
First-line antibiotic treatment for eradicating Helicobacter pylori (HP) infection is effective in HP-positive low-grade gastric mucosa-associated lymphoid tissue lymphoma (MALToma), but its role in HP-negative cases is uncertain. In this exploratory retrospective study, we assessed the outcome and potential predictive biomarkers for 25 patients with HP-negative localized gastric MALToma who received first-line HP eradication (HPE) therapy. An HP-negative status was defined as negative results on histology, rapid urease test, 13C urea breath test, and serology. We observed an antibiotic response (complete remission [CR], number = 8; partial remission, number = 1) in 9 (36.0%) out of 25 patients. A t(11;18)(q21;q21) translocation was detected in 7 (43.8%) of 16 antibiotic-unresponsive cases, but in none of the 9 antibiotic-responsive cases (P = 0.027). Nuclear BCL10 expression was significantly higher in antibiotic-unresponsive tumors than in antibiotic-responsive tumors (14/16 [87.5%] vs. 1/9 [11.1%]; P = 0.001). Nuclear NF-κB expression was also significantly higher in antibiotic-unresponsive tumors than in antibiotic-responsive tumors (12/16 [75.0%] vs. 1/9 [11.1%]; P = 0.004). A substantial portion of patients with HP-negative gastric MALToma responded to first-line HPE. In addition to t(11;18)(q21;q21), BCL10 and NF-κB are useful immunohistochemical biomarkers to predict antibiotic-unresponsive status in this group of tumors.
Highlights
Most low-grade gastric mucosa-associated lymphoid tissue lymphomas (MALT lymphomas) are characterized by close association with Helicobacter pylori (HP) infection, and eradication of HP can cure approximately 70% of these tumors1–4
We reported that HP cytotoxin-associated gene A (CagA) protein and its signaling pathway proteins, such as phospho (p)-SHP2, p-extracellular signal-regulated kinase (ERK), p-38 mitogen-activated protein kinase (MAPK), BCL-2, and BCL-XL, can be detected in tumors of gastric MALT lymphoma39,40
We demonstrated that nine (36.0%) out of 25 patients with HP-negative gastric MALT lymphoma were responsive to HP eradication (HPE), and remained lymphoma-free and progression-free at the longest follow-up
Summary
Most low-grade gastric mucosa-associated lymphoid tissue lymphomas (MALT lymphomas) are characterized by close association with Helicobacter pylori (HP) infection, and eradication of HP can cure approximately 70% of these tumors. Previous sporadic reports have revealed that certain types of HP-negative gastric MALT lymphomas can respond to common regimens that are used for HP eradication (HPE) therapy, i.e., a proton-pump inhibitor (PPI) plus clarithromycin, amoxicillin, metronidazole, or other antibiotics. Previous sporadic reports have revealed that certain types of HP-negative gastric MALT lymphomas can respond to common regimens that are used for HP eradication (HPE) therapy, i.e., a proton-pump inhibitor (PPI) plus clarithromycin, amoxicillin, metronidazole, or other antibiotics9–11 As mentioned in these reports, some HP-negative patients might still have HP-associated tumors because previous use of bismuth, PPIs, and antibiotics could lead to pseudo-negative results on conventional HP tests such as the rapid urease test, the urea breath test, and histology. The expression of CagA and CagA-signaling molecules is closely associated with HP-dependence of these tumors, indicating CagA may serve as a marker for the presence of HP for gastric MALT lymphoma
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