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

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2621-2621
Author(s):  
Xiao-Yan Ke ◽  
Jing Wang ◽  
Ling-Zhi Zhao ◽  
Zi-Fen Gao ◽  
Fei Dong ◽  
...  

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.

Blood ◽  
2001 ◽  
Vol 98 (4) ◽  
pp. 1182-1187 ◽  
Author(s):  
Hongxiang Liu ◽  
Hongtao Ye ◽  
Ahmet Dogan ◽  
Renzo Ranaldi ◽  
Rifat A. Hamoudi ◽  
...  

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.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 982-982
Author(s):  
Hongtao Ye ◽  
Liping Gong ◽  
Hongxiang Liu ◽  
Agnes Ruskone-Fourmestraux ◽  
Daphne de Jong ◽  
...  

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.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2424-2424 ◽  
Author(s):  
Noriko Fukuhara ◽  
Hiroyuki Tagawa ◽  
Tsuneya Nakamura ◽  
Hiroshi Inagaki ◽  
Yasuo Morishima ◽  
...  

Abstract Background: Approximately 70% of low grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma cases are successfully treated by H. pylori eradication. The MALT lymphoma resistant to this therapy needs an additional therapy. A part of the tumors transform to an aggressive lymphoma including diffuse large B-cell lymphoma (DLBCL). The t(11;18)(q21;q21) characteristic to MALT lymphoma is recognized as a marker for H. pylori independency, but this marker is found in only a half of the MALT lymphomas resistant to H. pylori eradication. Therefore the detailed genomic features of eradication resistant group as well as dependent group are needed to understand molecular basis. Patients and Methods: We performed array-based comparative genomic hybridization for 30 gastric MALT lymphomas treated with H. pylori eradication. These included 10 cases of t(11;18)(q21;q21)-positive MALT group, 10 cases of t(11;18)(q21;q21)-negative MALT with H. pylori dependent group and 10 cases of t(11;18)(q21;q21)-negative MALT with H. pylori independent group. The presence of t(11;18)(q21;q21) was identified by a multiplex reverse transcriptase polymerase chain reaction of the API2-MALT1 chimeric transcript. Results: Almost no significant genetic alterations were found in t(11;18)(q21;q21)-positive MALT lymphoma, whereas numerous genomic alterations were found in those without t(11;18)(q21;q21). These aberrations were mostly similar to those found in DLBCL (Tagawa et al., Blood 106:5, 2005). Trisomy 3 is most recurrent and 7q loss specific to SMZL is also recurrent. Within the t(11;18)(q21;q21)-negative MALT lymphoma group, presence of genomic imbalances is more frequent in H. pylori independent group (one of ten (10%) vs seven of ten (70%); p =0.019, two-sided fisher’s exact test). Neither locally advanced disease nor including large cell component is correlated with H. pylori independency, respectively. Conclusions: Genomic imbalances are associated with H. pylori independency in t(11;18)(q21;q21)-negative gastric MALT lymphomas. Thus, the genomic imbalances may have a role in the acquisition of H. pylori-independent growth.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5010-5010
Author(s):  
Takakazu Kawase ◽  
Keitaro Matsuo ◽  
Tsuneya Nakamura ◽  
Junya Kanda ◽  
Hidemi Ito ◽  
...  

Abstract Abstract 5010 Extranodal marginal zone B-cell lymphoma of mucosaassociated lymphoid tissue (MALT Lymphoma) is low-grade extranodal lymphoma, and it comprises 7-8% of all B cell lymphomas, and up to 50% of primary gastric lymphoma. It is known that a preexisting chronic inflammation such as Helicobactoer pylori (H. pylori) gastritis can influence its development, however, some MALT lymphomas with no evidence of such inflammation are found. Protracted remissions may be induced by H. pylori eradication therapy, but cases with t(11;18)(q21;q21) appear to be resistant to the therapy. t(11;18)(q21;q21) has been observed in 25-50% of the cases and API2 at 11q21 and MALT1 at 18q21 are fused as a result of this translocation. Thus, API2-MALT1 fusion positive and negative MALT lymphoma may have different etiology, although histological features of both MALT lymphomas have not been clearly delineated. To clarify differences of epidemiological features between API2-MALT1 fusion positive and negative gastric MALT lymphoma, we conducted a case-control study of 61 newly and histologically diagnosed gastric MALT lymphoma cases (14 of API2-MALT1 fusion positive cases and 47 of negative cases) and 610 age and sex frequency-matched non-cancer controls. API2-MALT1 fusion was evaluated by a multiplex reverse transcription-polymerase chain reaction using formalin-fixed, paraffinembedded sections. We evaluated the association with alcohol intake (never drinkers, occasional drinkers, and frequent but moderate (<50 g/day of alcohol) and frequent and heavy drinkers (≥50 g/day of alcohol)), smoking (<5, 5-19, 20-39, ≥40 pack-years), past history of gastroduodenal ulcer, height, and risk of API2-MALT1 fusion positive and negative gastric MALT lymphoma. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using multinomial logistic models adjusted for potential confounders. A significant association was observed between past history of gastroduodenal ulcer and the risk only among fusion negative cases, with ORs of subjects with past history of gastroduodenal ulcer of 2.86 (95% CI, 1.31-6.14; p = 0.008) compared to subjects without past history of gastroduodenal ulcer. No clear associations were observed between alcohol intake, smoking, height and the risk irrespective of positivity of API2-MALT1 fusion. These findings suggest that past history of gastroduodenal ulcer, which may be due to H.pylori infection, does not associated with the carcinogenic mechanism of API2-MALT1 fusion positive gastric MALT lymphoma, and fusion positive and negative tumors have different etiology. Further investigations using large data sets are needed. Disclosures No relevant conflicts of interest to declare.


2018 ◽  
Vol 11 (3) ◽  
pp. 187-193 ◽  
Author(s):  
Petruta Violeta Filip ◽  
◽  
Denisa Cuciureanu ◽  
Laura Sorina Diaconu ◽  
Ana Maria Vladareanu ◽  
...  

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.


2013 ◽  
pp. 154-158
Author(s):  
Angelo Zullo ◽  
Cesare Hassan ◽  
Francesca Cristofari ◽  
Claudia Iegri ◽  
Nicoletta Villiva ◽  
...  

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.


2018 ◽  
Vol 25 (1) ◽  
pp. 107327481877825 ◽  
Author(s):  
Luis Miguel Juárez-Salcedo ◽  
Lubomir Sokol ◽  
Julio C. Chavez ◽  
Samir Dalia

Primary gastric lymphoma (PGL) is the most common extranodal non-Hodgkin lymphoma and represents a wide spectrum of disease, ranging from indolent low-grade marginal zone lymphoma or mucosa-associated lymphoid tissue (MALT) lymphoma to aggressive diffuse large B-cell lymphoma. The PGL is a relatively rare cancer and easily misdiagnosed due to its unspecific symptoms of the digestive tract. The medical literature and ongoing clinical trials were reviewed on the clinical presentation, diagnosis, prognosis, prevention, and treatment of PGL. Primary gastric lymphoma is an event in the course of cancer with a variable clinical presentation and a wide differential diagnosis. Chronic gastritis secondary to Helicobacter pylori ( H pylori) infection has been considered a major predisposing factor for MALT lymphoma. Magnetic resonance imaging and endoscopic ultrasonography have helped in staging of these cancers. The clinical course and prognosis of this disease are dependent on histopathological subtype and stage at the time of diagnosis. A global therapeutic approach to the cure of PGL has completely changed over the past 10 years, including innovative and conservative options to reduce treatment toxicity. Due to the rarity of PGL, many aspects of this neoplasm are still controversial. The incidence of this disease is increasing, making it necessary for clinicians to understand the clinical symptoms, workup, and treatment of these lymphomas.


2018 ◽  
Vol 113 (Supplement) ◽  
pp. S937-S938
Author(s):  
Gurjiwan S. Virk ◽  
Jennifer Copare ◽  
Sven Hida ◽  
Seth J. Richter

Blood ◽  
1995 ◽  
Vol 85 (8) ◽  
pp. 2000-2004 ◽  
Author(s):  
AC Wotherspoon ◽  
TM Finn ◽  
PG Isaacson

Characteristic chromosomal aberrations have been associated with subtypes of non-Hodgkin's lymphoma with distinct clinicopathologic features. Low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) form such a group and might be expected to be characterized by a specific cytogenetic abnormality. Metaphase analyses of MALT lymphoma are rare due to problems with fresh tissue collection and poor in vitro proliferation. However, the small number of published series suggests that chromosome trisomies, particularly trisomy 3, might be characteristic of these tumors. The application of interphase cytogenetic techniques to routinely processed material allows the examination of a large series of archival cases and is particularly useful for the demonstration of chromosome trisomies. We have used this technique to analyze 70 cases of low-grade MALT lymphoma from various sites and found trisomy 3 in 60%. This finding compares with 16% in low-grade nodal B-cell lymphoma and 27% in primary splenic lymphoma of marginal zone type (splenic lymphoma with villous lymphocytes). These results provide further evidence that low-grade MALT lymphomas from all sites form a single pathologic entity distinct from nodal B-cell lymphomas. Although MALT lymphoma and primary splenic lymphoma may arise from marginal zone B cells, they are genetically distinct.


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