Strong BCL10 Nuclear Expression Identifies Gastric MALT Lymphomas That Do Not Respond to H. pylori Eradication.

Abstract Purpose: In a previous retrospective study, we have shown that 75% of gastric MALT lymphomas that did not respond to H. pylori eradication could be identified by detection of t(11;18)(q21;q21). The present study examined the value of t(1;14)(p22;q32) in prediction of the response of gastric MALT lymphomas to H. pylori eradication. Patients and Methods: A total of 111 patients with H. pylori-positive gastric MALT lymphoma, who were treated by H. pylori eradication, were screened for BCL10 involved chromosome translocation by BCL10 immunohistochemistry, followed by interphase FISH and real-time quantitative reverse transcription PCR (qRT-PCR). The clinical presentation of 11 cases of MALT lymphoma including 6 from the stomach with known BCL10 involved chromosome translocation was reviewed. Results: Of the 111 cases of gastric MALT lymphoma treated by H. pylori eradication, 75 including 35 from the complete regression group and 40 from the non-responsive group, had adequate specimens for BCL10 immunohistochemistry. Two cases showed strong BCL10 nuclear staining in virtually all tumor cells, similar to that seen in those with t(1;14)(p22;q32). Both were from the H. pylori eradication non-responsive group. Although interphase FISH failed to show evidence of BCL10 gene break or amplification, one case showed an IGH break. This case also showed a high level of BCL10 mRNA expression, compatible to that seen in MALT lymphoma with t(1;14)(p22;q32). 9 of the 11 cases with known BCL10 involved translocation were at stage IIE or above, with three showing agressive clinical presentations. Conclusion: Gastric MALT lymphomas with strong BCL10 nuclear expression or t(1;14)(p22;q32) are mostly likely resistant to H. pylori eradication.

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Higher Rates of t(11;18) in Chinese Patients with Transformed Type of MALT Lymphoma Suggest Novel Pathways for Progression of the Disease.

Blood ◽

10.1182/blood.v110.11.2621.2621 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2621-2621

Author(s):

Xiao-Yan Ke ◽

Jing Wang ◽

Ling-Zhi Zhao ◽

Zi-Fen Gao ◽

Fei Dong ◽

...

Keyword(s):

Malt Lymphoma ◽

B Cell Lymphoma ◽

Chromosome Translocation ◽

Chinese Patients ◽

Low Grade ◽

Fixed Tissue ◽

Detection Rates ◽

Nuclear Expression ◽

H Pylori ◽

Selection Of

Abstract Previous reports suggest that the prevalence and potential etiological factors of some types of lymphoma in China may be different from that reported in other countries. Our previous work in analyzing cell origin of 53 diffuse large B-cell lymphoma (DLBCL) patients demonstrated that Chinese patients have higher Non GC (%) DLBCL than GC(%) origin compare with the reports from Western countries (PMID: 16202261). In this study, we continued our exploration on potential differences between Chinese patients with mucosa-associated lymphoid tissue (MALT) lymphoma and patients reported from other countries. Several evidences suggest that gastric MALT lymphoma acquired as a consequence of Helicobacter pylori (H. pylori) infection and 80–90% patients with no t(11;18) chromosome translocation achieved the complete remission (CR) after receiving antibiotics therapy to eradicate H. pylori. But the patients with MALT, who have the t(11;18) and the nuclear expression of BCL-10, are barely responsive to the antibiotic therapy. Therefore, detection of the expression of t(11; 18) and BCL-10 nuclear expression in the patients with MALT lymphoma is of clinical significance in selection of H. pylori eradication regimen, predicting the clinical progression, and assessing the prognoses of the disease. In this study, we detected the t(11;18) chromosome translocation in different stages of MALT lymphoma. We established a RT-PCR with a method of short-length amplification by modifying that reported in preparation of RNAs from the paraffin-fixed tissue followed by molecular analysis of the genotype of the patients with MALT lymphoma. We examined the expression of API2-MALT1 in a large cohort of patients with lymphomas including 100 MALT lymphomas and 83 DLBCL cases, and analyzed the differences in the detection rates of API2-MALT1 fusion transcripts and BCL-10 nuclear expression among different MALT location. Our results showed the five key findings, including higher detection rates of t(11;18) (21.13%) in Chinese patients with transformed MALT lymphoma, lower detection rates of t(11;18) (15.79%) in stomach MALT lymphoma, different organ localizations of MALT lymphoma in Chinese patients, higher nuclear expression rates of Bcl-10 in low grade MALT (51.72%), and lower response rates (50% CR, and 50% PR) to anti-H. pylori therapy, suggest novel pathways for low-grade MALT lymphoma to be progressed into transformed MALT lymphoma. This study also suggests that amplification of shorter length of PCR products from the paraffin-fixed tissues increases the sensitivity, which is significant in improving selection of therapeutic regimen and assessing the prognoses of disease. Also, in Chinese patients with MALT lymphoma, Bcl-10 nuclear expression may be independent of t(11;18) translocation, and may also play primary roles in MALT pathogenesis rather than “supporting roles” for t(11;18). Future international collaboration is needed to clarify that whether this new model fits patients with other ethnic backgrounds in addition to Chinese patients.

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BCL10 aberations and NF-kappa B activation involving p65 are absent or rare in primary gastric MALT lymphoma

Vojnosanitetski pregled ◽

10.2298/vsp130813035h ◽

2014 ◽

Vol 71 (11) ◽

pp. 1040-1044 ◽

Cited By ~ 1

Author(s):

Jelena Hajder ◽

Dragomir Marisavljevic ◽

Natasa Stanisavljevic ◽

Biljana Mihaljevic ◽

Vladimir Kovcin ◽

...

Keyword(s):

Tumor Cells ◽

Malt Lymphoma ◽

Treatment Options ◽

Signal Pathways ◽

Gastric Malt Lymphoma ◽

Common Symptom ◽

Nf Kappa B ◽

Nuclear Expression ◽

Nf Kappab ◽

H Pylori

Bacground/Aim. Mucosa-associated lymphoid tissue (MALT) lymphoma accounts for 5-17% non-Hodgkin lymphomas (NHL). The molecular pathogenesis of MALT lymphomas is not well-established. The aim of this study was to evaluate immunohistochemically determined nuclear coexpression of BCL10 and NF-kappaB (NF-?B) in tumor cells of gastric MALT lymphoma and its impact on the patogenesis and outcome of the disease. Methods. Medical records of 35 patients with newly diagnosed gastric MALT lymphoma were analyzed and biopsy specimens were immunostained for BCL10 and NF-kB expression (p65 subunit). Results. The median age of 35 patients diagnosed with gastric MALT lymphoma was 63.5 years (male/female = 21/14). Symptoms were present in 23/35 (65.7%) patients with the weight loss as the most common symptom. Gastric MALT lymphomas were usually localized in the stomach corpus and corpus and antrum (45.7% and 31.2%, respectively). H. pylori infection was confirmed in 20 out of 30 (66.7%) patients. Treatment options were as follows: immunochemotherapy in 10 (28.5%) patients, surgery in 9 (25.8%) patients, combined surgery and chemotherapy in 14 (40%) patients and supportive measures in 2 (5.7%) patients. Complete remission was achieved in 13 (37.1%) patients and partial remission in two (5.7%) patients. Sixteen (45.7%) patients had disease progression (p < 0.001). Cytoplasmatic expression of BCL10 in tumor cells was detected in 19 (54.3%) specimens. Nuclear expression was detected in no specimen. Cytoplasmic expression of NF-?B was present in 22 (65.7%) specimens, but nuclear expression was not detected in any specimens. Conclusion. Nuclear expressions (activation) of NF-?B p65 subunit and BCL10 were not detected in specimens of gastric MALT lymphoma. The correlation of nuclear coexpression of BCL10 and NF-?B in gastric MALT lymphoma was not established. These results indicate that other mechanisms and signal pathways are active in lymphogenesis of gastric MALT lymphoma, as that apoptotic inhibition is not the main, nor the only mechanism in tumorogenesis.

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Patients with gastric MALT lymphoma revealing persisting endoscopic abnormalities after successful eradication of Helicobacter pylori can be safely managed by a watch-and-wait strategy

Zeitschrift für Gastroenterologie ◽

10.1055/a-0859-7737 ◽

2019 ◽

Vol 57 (05) ◽

pp. 593-599

Author(s):

Wolfgang Fischbach ◽

Christian Dorlöchter

Keyword(s):

Helicobacter Pylori ◽

Malt Lymphoma ◽

Single Case ◽

Gastric Malt Lymphoma ◽

Complete Regression ◽

Watch And Wait ◽

Oncological Treatment ◽

First Line Therapy ◽

Diffuse Atrophy ◽

H Pylori

Abstract Background In current guidelines, Helicobacter pylori eradication is recommended as first-line therapy in patients with gastric MALT lymphoma. This leads to complete lymphoma regression in the majority of patients. Those who show persisting histological residuals of lymphoma after eradication of the bacterium and normalization of endoscopic findings are managed by a watch-and-wait strategy. We aim to show that such an approach can be extended to patients with persisting endoscopic abnormalities. Methods Thirteen patients (7 female and 6 male; 62 years, range: 43 – 80) with gastric MALT lymphoma of stages I and II1 had received exclusive H. pylori eradication. Control endoscopies performed every 3 – 4 months during the first 2 years and 6 and 12 times monthly 2 – 5 and > 5 years after diagnosis, respectively, revealed successful eradication of H. pylori but persisting endoscopic abnormalities. Histologically, complete regression of the lymphoma or minor residuals were observed. Results Persisting endoscopic changes included thickened folds with or without superficial erosions, nodular mucosal surface with or without angiectasia, focal or diffuse atrophy, focal erythema, or a mixture of these findings. During a follow-up of 89.9 (12 – 329) months, the outcome of these patients was excellent with no single case of lymphoma progression. Conclusion A watch-and-wait strategy can be recommended for patients with gastric MALT lymphoma showing persisting endoscopic abnormalities after eradication of H. pylori. There is no need for any oncological treatment provided that regular endoscopic-bioptic controls do not reveal any progressive changes. A standardized description of the endoscopic changes as well as a thorough bioptic technique should be included.

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Genetic Characterization and Clinical Features of Helicobacter pylori Negative Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Cancers ◽

10.3390/cancers13122993 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2993

Author(s):

Barbara Kiesewetter ◽

Christiane Copie-Bergman ◽

Michael Levy ◽

Fangtian Wu ◽

Jehan Dupuis ◽

...

Keyword(s):

Gastric Mucosa ◽

Signaling Pathways ◽

Clinical Features ◽

Malt Lymphoma ◽

Lymphoid Tissue ◽

Targeted Sequencing ◽

Clinicopathological Parameters ◽

Gastric Malt Lymphoma ◽

Genetic Changes ◽

H Pylori

Background: In Western countries, the prevalence of gastric mucosa-associated lymphoid tissue (MALT) lymphoma has declined over the last three decades. Contemporaneously, H. pylori negative gastric MALT lymphoma is increasingly encountered, and their genetic basis and clinical features remain elusive. Methods: A total of 57 cases of H. pylori negative gastric MALT lymphoma were reviewed and investigated for chromosome translocation by fluorescence in-situ hybridization and for somatic mutations by the targeted sequencing of 93 genes. Results: MALT1 translocation, most likely t(11;18)(q21;q21)/BIRC3-MALT1, was detected in 39% (22/57) cases, and IGH translocation was further seen in 12 MALT1-negative cases, together accounting for 60% of the cohort. Targeted sequencing was successful in 35 cases, and showed frequent mutations in NF-κB signaling pathways (TNFAIP3 = 23%, CARD11 = 9%, MAP3K14 = 9%), together affecting 14 cases (40%). The NF-κB pathway mutations were mutually exclusive from MALT1, albeit not IGH translocation, altogether occurring in 86% of cases. There was no significant correlation between the genetic changes and clinicopathological parameters. The patients showed a median of progression-free survival (PFS) of 66.3 months, and a significant superior PFS when treated with systemic versus antibiotic therapy (p = 0.004). Conclusion: H. pylori negative gastric MALT lymphoma is characterized by highly frequent genetic changes in the NF-κB signaling pathways.

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MALT lymphoma: epidemiology, clinical diagnosis and treatment

Journal of Medicine and Life ◽

10.25122/jml-2018-0035 ◽

2018 ◽

Vol 11 (3) ◽

pp. 187-193 ◽

Cited By ~ 13

Author(s):

Petruta Violeta Filip ◽

◽

Denisa Cuciureanu ◽

Laura Sorina Diaconu ◽

Ana Maria Vladareanu ◽

...

Keyword(s):

Helicobacter Pylori ◽

B Cell ◽

Malt Lymphoma ◽

Cell Lymphoma ◽

Gastric Lymphoma ◽

Eradication Therapy ◽

B Cell Lymphoma ◽

Gastric Malt Lymphoma ◽

H Pylori

Primary gastric lymphoma (PGL) represents a rare pathology, which can be easily misdiagnosed because of unspecific symptoms of the digestive tract. Histologically, PGL can vary from indolent marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) to aggressive diffuse large B-cell lymphoma (DLBCL). During the years, clinical trials revealed the important role of Helicobacter pylori (H. pylori) in the pathogenesis of gastric MALT lymphoma. Infection with Helicobacter pylori is an influential promoter of gastric lymphomagenesis initiation. Long-term studies revealed that eradication therapy could regress gastric lymphomas.

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Can we eradicate gastric MALT-lymphoma?

Italian Journal of Medicine ◽

10.4081/itjm.2010.154 ◽

2013 ◽

pp. 154-158

Author(s):

Angelo Zullo ◽

Cesare Hassan ◽

Francesca Cristofari ◽

Claudia Iegri ◽

Nicoletta Villiva ◽

...

Keyword(s):

Malt Lymphoma ◽

Early Stage ◽

Gastric Lymphoma ◽

Survival Rates ◽

Antibody Therapy ◽

Gastric Malt Lymphoma ◽

Low Grade ◽

Success Rates ◽

H Pylori

The incidence of primary gastric lymphoma in Italy is considerably higher than that observed in the rest of Europe. It is widely accepted that gastric B-cell, low-grade mucosalassociated lymphoid tissue (MALT) lymphoma is caused by specific host-bacterial interactions that occur during Helicobacter pylori infection. This review examines recent findings on the origins, diagnosis, treatment, and follow-up of gastric MALT lymphomas. Clinical and endoscopic findings at diagnosis vary widely. In a substantial number of cases, the patient presents only vague dyspeptic symptoms or poorly defined abdominal pain with no macroscopic lesions on the gastric mucosa. Review of data from 32 trials in which a total of 1,387 MALT-lymphoma patients of the stomach were treated solely with H. pylori eradication revealed high remission rates when the disease is treated early (stage I-II1). Neoplasia confined to the submucosa, antral localization of tumors, and negativity for the API2-MALT1 translocation were associated with a high probability of remission following H. pylori eradication. When the latter approach is not sufficient, radiotherapy, chemotherapy and, in selected cases, surgery are associated with high success rates; data on the efficacy of monoclonal antibody therapy (rituximab) are still limited. Five-year survival rates are higher than 90%. Patients whose tumors have been eliminated require close, long-term endoscopic follow-up since recurrence has been reported in some cases. Broader clinical follow-up is also advisable because the incidence of other solid tumors and of cardiovascular events is reportedly increased in these patients.

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T(11;18)(q21;q21) is associated with advanced mucosa-associated lymphoid tissue lymphoma that expresses nuclear BCL10

Blood ◽

10.1182/blood.v98.4.1182 ◽

2001 ◽

Vol 98 (4) ◽

pp. 1182-1187 ◽

Cited By ~ 172

Author(s):

Hongxiang Liu ◽

Hongtao Ye ◽

Ahmet Dogan ◽

Renzo Ranaldi ◽

Rifat A. Hamoudi ◽

...

Keyword(s):

Malt Lymphoma ◽

Lymphoid Tissue ◽

Fusion Transcript ◽

Low Grade ◽

Chain Reaction ◽

Nuclear Expression ◽

Molecular Events ◽

Multistep Process ◽

Polymerase Chain ◽

H Pylori

The development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a multistep process and can be clinico-pathologically divided into Helicobacter pylori-associated gastritis, low-grade tumors, and high-grade tumors. The molecular events underlying this progression are largely unknown. However, identification of the genes involved in MALT lymphoma-specific t(11;18)(q21;q21) and t(1;14)(p22;q32) has provided fresh insights into the pathogenesis of this disease. T(11;18)(q21;q21) results in a chimeric transcript between the API2 and theMALT1 genes, whereas t(1;14) (p22;q32) causes aberrant nuclear BCL10 expression. Significantly, nuclear BCL10 expression also occurs frequently in MALT lymphomas without t(1;14)(p22;q32), suggesting an important role for BCL10 in lymphoma development. Thirty-three cases of H pylori gastritis, 72 MALT lymphomas, and 11 mucosal diffuse large B-cell lymphomas (DLBCL) were screened for t(11;18)(q21;q21) by reverse transcription–polymerase chain reaction followed by sequencing. BCL10 expression in lymphoma cases was examined by immunohistochemistry. The API2–MALT1 fusion transcript was not detected in H pylorigastritis and mucosal DLBCL but was found in 25 of 72 (35%) MALT lymphomas of various sites. Nuclear BCL10 expression was seen in 28 of 53 (53%) of MALT lymphomas. Of the gastric cases, the largest group studied, the frequency of both t(11;18)(q21;q21) and nuclear BCL10 expression was significantly higher in tumors that showed dissemination to local lymph nodes or distal sites (14 of 18 = 78% and 14 of 15 = 93%, respectively) than those confined to the stomach (3 of 29 = 10% and 10 of 26 = 38%). Furthermore, t(11;18)(q21;q21) closely correlated with BCL10 nuclear expression. These results indicate that both t(11;18)(q21;q21) and BCL10 nuclear expression are associated with advanced MALT lymphoma and that their oncogenic activities may be related to each other.

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Long-Term Clinical Outcomes of Gastric MALT Lymphoma: A Nationwide Multicenter Study in Korea

Frontiers in Oncology ◽

10.3389/fonc.2021.681689 ◽

2021 ◽

Vol 11 ◽

Author(s):

Joon Sung Kim ◽

Jun Chul Park ◽

Jong Yeul Lee ◽

Ji Yong Ahn ◽

Sun Hyung Kang ◽

...

Keyword(s):

Overall Survival ◽

Malt Lymphoma ◽

Case Series ◽

Stage Iii ◽

Gastric Malt Lymphoma ◽

University Hospitals ◽

Initial Stage ◽

Testing Stage ◽

H Pylori

BackgroundTreatment recommendations for gastric mucosa-associated lymphoid tissue (MALT) lymphoma are based on case series and expert opinions. Only a few previous studies have focused on the long-term outcomes of gastric MALT lymphoma, especially according to stage.MethodsPatients diagnosed with gastric MALT lymphoma from January 2000 to December 2018 at nine university hospitals in Korea were included. Clinical data of medical history, endoscopic features, histological diagnosis, results of Helicobacter pylori (H. pylori) testing, stage, treatment conditions, and outcomes were collected.ResultsA total of 1,163 patients was enrolled, and 97.6% (n=1,038) of patients were diagnosed as stage IE. 10-year overall survival (OS) for the entire population was 99.1% and was better for patients in stage IE compared with patients in stage III/IV (p=0.002). The 10-year OS for H. pylori-positive patients was better than that of H. pylori-negative patients (p=0.022). Multivariate analyses revealed initial stage III/IV as a prognostic factor associated with over-all survival.ConclusionThe majority of gastric MALT lymphoma patients are diagnosed at an early localized stage in Korea. The overall survival rate of gastric MALT lymphoma is excellent and is associated with the initial stage of the disease.

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