First-line antibiotic therapy in Helicobacter pylori-negative low-grade gastric mucosa-associated lymphoid tissue lymphoma

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.

Figure 1

Immunohistochemical analysis of CagA expression in tumor cells of HP-negative gastric MALT lymphoma. (a) An antibiotic-responsive case (Case 9#, time to complete remission [CR] after completing HPE, 5 months) displaying no CagA expression in the tumor cells of the gastric mucosa (b) An antibiotic-responsive case (Case 19#, time to CR after completing HPE, 10 months) displaying no CagA expression in the tumor cells of the gastric mucosa (c) An antibiotic-responsive case (Case 23#, time to CR after completing HPE, 4 months) displaying no CagA expression in the tumor cells of the gastric mucosa (d) An antibiotic-responsive case of HP-positive gastric MALT lymphoma (time to CR after completing HPE, 1 month) displaying nuclear CagA expression in the tumor cells of the gastric mucosa (served as positive control).

Figure 2

Endoscopic features and immunohistochemical analysis of BCL10 and NF-κB expression in HP-negative gastric MALT lymphoma. (a) Endoscopy showing a 2 cm slightly raised lesion with hyperemic patches in the antrum of the stomach of a 51-year-old woman (Case 22#). (b) One month after the completion of an HPE regimen, CR was achieved. (c) Endoscopy showing elevated and enlarged folds lesions measuring about 3~4 cm in the upper body of a 59-year-old woman. Right upper bottom, endoscopic ultrasound showing tumor with mucosa involvement (thickness up to 7.2 mm at second layer) (Case #15). (d) Four months after the completion of an HPE regimen, partial remission was achieved. (e) Nuclear expression of BCL10 in tumor cells of an antibiotic-unresponsive case (Case #6). (f) Nuclear expression of NF-κB in tumor cells of an antibiotic-unresponsive case (Case #6). HPE, H. pylori eradication therapy.

Figure 3

The time to complete remission of patients with antibiotic-responsive tumors. (a) Time to CR in our 8 cases was calculated from the completion of antibiotic treatment to the first evidence of CR through Kaplan–Meier analysis. (b) Time to CR in 26 cases of our series and that of five other investigators (refs^,,,,) was calculated from the completion of antibiotic treatment to the first evidence of CR through Kaplan–Meier analysis. Mo, month; CI, confidence interval; HPE, H. pylori eradication therapy.