The gastric marginal zone B-cell lymphoma of MALT type.
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Antineoplastic Agents↗
Biomedical subjects
E Zucca
Publications and source records attributed to E Zucca.
Analysis of Fas/CD95 gene somatic mutations in ovarian cancer cell lines.
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Apoptosis↗
Association of gastric and Waldeyer's ring lymphoma: a molecular study.
The coexistence of Waldeyer's ring and gastrointestinal non-Hodgkin's lymphomas at presentation is well known. Moreover, localized gastrointestinal relapses following successful treatment of lymphomas of Waldeyer's ring and thyroid lymphomas occurring after a prolonged disease-free interval have also been described. We report two cases of concomitant lymphoma in Waldeyer's ring and stomach. On the basis of the molecular analysis of the immunoglobulin heavy chain gene rearrangements, two different patterns of concomitant involvement by a lymphoma in Waldeyer's ring and in the gastrointestinal region seem to exist. One is represented by the preferential dissemination of the lymphoma from one site to the other, the second by the apparently independent growth of clonally unrelated lymphomas at each site.
Complementarity Determining Regions↗
Prognostic models for diffuse large B-cell lymphoma.
Prognosis of DLCL patients is variable and associated with well-defined risk factors. In the past decade several pretreatment variables have been incorporated into prognostic models to predict the death risk of individual patients. The International Prognostic Index (IPI), developed in an international consensus study, has been one of the most widely accepted of these models. In our study we applied some of the major prognostic models proposed for DLCLs in a cohort of 111 patients uniformly treated with a CHOP-like regimen in order to compare their sensitivity and specificity. We also evaluated the possibility of improving the IPI with the inclusion, from among the variables analysed, of serum beta-2 microglobulin level (beta-2M). The sensitivity, reflecting the ability to predict all failures in the cohort of patients as a whole, has improved from 45 to 73 per cent when the beta-2M-IPI model is compared with IPI, without a significant loss of specificity. Based on these results, the beta-2M-IPI may be useful for identifying the subset of patients with very poor prognoses. Therefore, the use of the serum beta-2M value in addition to the IPI may help in selection of the patients with DLCL at higher risk for treatment failure, and identification of those who may require specifically tailored therapeutic approaches.
Adult↗
Eradication of Borrelia burgdorferi infection in primary marginal zone B-cell lymphoma of the skin.
Primary cutaneous B-cell lymphomas have been associated with Borrelia burgdorferi, the spirochete responsible for Lyme disease. Recently, cutaneous marginal zone B-cell lymphoma has been proposed as a distinct clinical-pathological entity. We report a case of primary cutaneous marginal zone lymphoma, associated with B burgdorferi infection. Polymerase chain reaction (PCR) amplification of the third complementarity determining region (CDR3) of the immunoglobulin heavy chain gene showed the presence of a monoclonal lymphoproliferation, therefore strengthening the histological diagnosis of a malignant process. B burgdorfer-specific hbb gene sequences were detected by PCR in the lymphoma tissue at diagnosis but not after antibiotic treatment. A nearly complete clinical and histological regression was observed after B burgdorferi eradication, with immunohistochemistry studies showing disappearance of plasma cell differentiation and a marked decline in the number of CD3+ T cells and Ki-67+ cells. Our case confirms the link between B burgdorferi and some cutaneous lymphomas. The disappearance of the microorganism accompanied by the unequivocal decrease of most indicators of active T- and B-cell immune response strongly supported a pathogenetic role for B burgdorferi in sustaining an antigen-driven development and growth of this cutaneous marginal zone lymphoma. Antibiotic therapy (analogous to Helicobacter pylori infection in gastric MALT lymphoma) might be helpful with the aim of averting or at least deferring the indication for more aggressive treatment.
Aged↗
Molecular detection of circulating neoplastic cells in patients with clinically localised gastric and non-gastric mucosa-associated lymphoid tissue lymphoma.
BACKGROUND: Unlike other low-grade lymphomas, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type usually presents with localised disease. AIM: To detect peripheral blood lymphoma involvement to establish the incidence of occult lymphoma dissemination. PATIENTS AND METHODS: In a series of 18 cases, peripheral blood was analysed by polymerase chain reaction, with primers directed to the third-complementarity determining region of the immunoglobulin heavy chain gene. RESULTS AND CONCLUSION: The presence of circulating neoplastic cells was detected in 21% of clinically localised cases. Moreover lymphoma cells were detected in 2 out of 6 morphologically normal bone marrow specimens. The present data show that, combining morphological and molecular methods, occult dissemination can be found in a large proportion of cases thus stressing the need for careful staging procedures. However, it has still to be clarified whether the presence of polymerase chain reaction-detectable circulating lymphoma cells can influence the outcome of mucosa-associated lymphoid tissue lymphoma patients submitted to antibiotic treatment (for gastric localisation) or local therapy (surgery or radiation, for non-gastric tumours).
Adult↗
Lack of CD95/FAS gene somatic mutations in extranodal, nodal and splenic marginal zone B cell lymphomas.
Germline CD95 (also known as FAS, APT1 and APO1) gene mutations have been associated with benign lymphoproliferative diseases and autoimmune processes. Somatic mutations have been reported in human tumours, including lymphomas. Since marginal zone B cell lymphomas usually arise in a background of chronic inflammation, often of autoimmune origin, we searched for CD95 gene mutations in an unselected series of marginal zone B cell lymphomas. The CD95/FAS full coding region, comprising exon-intron junctions, was amplified from genomic DNA by polymerase chain reaction (PCR) in 10 separate reactions. PCR products were analysed by single-strand conformation polymorphism (SSCP) and visualised by silver staining. Bands exhibiting an altered electrophoretic mobility were sequenced. Twenty-seven cases of marginal zone B cell lymphomas of whom fresh or frozen tumour material was available (18 extranodal, five splenic and four nodal) were studied. Previously described silent polymorphisms in exons 7 (C836T) and 3 (T416C) were detected in 42% and in 19% of the cases, respectively. One silent T-to-A substitution at bp 431, within exon 3, was found in one case. Our results did not reveal the presence of CD95 somatic mutations in unselected cases of marginal zone B cell lymphomas. On the basis of our data, we cannot rule out that other genes coding for proteins involved in the CD95-induced apoptotic pathway might be altered. However, this pathway does not seem to play an important role in the pathogenesis of these lymphoma subtypes.
Antigens, Neoplasm↗
BCL10 gene mutations rarely occur in lymphoid malignancies.
BCL10, a gene involved in apoptosis signalling, has recently been identified through the cloning of chromosomal breakpoints in extranodal (MALT-type) marginal zone lymphomas carrying the t(1;14)(p22;q32) translocation. BCL10 was also found mutated in these cases as well as in other types of lymphoid and solid tumors, suggesting that its inactivation may play an important pathogenetic role; however, this has been questioned by recent studies showing a lack of somatic mutations in human cancers. We report the mutation analysis of exons 1-3 of the BCL10 gene in DNAs from 228 cases of lymphoid malignancies (30 B cell chronic lymphocytic leukemias, 123 B and 45 T non-Hodgkin's lymphomas and 30 multiple myelomas). Somatic mutations were detected in four cases (approximately 2%): one small lymphocytic, one follicular and two diffuse large cell lymphomas. The mutations were all within exon 3 and have not been previously reported. Our data suggest that BCL10 mutations may play only a limited role in the pathogenesis of lymphoid neoplasms.
Adaptor Proteins, Signal Transducing↗
Extranodal lymphomas.
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Central Nervous System Neoplasms↗
Extranodal marginal zone B-cell lymphoma genotyping by Alu-polymerase chain reaction.
DNA amplification by polymerase chain reaction (PCR) with primers designed on the widely distributed Alu sequences allows the production of specific inter-Alu DNA-fingerprints. Amplification of tumour and matched normal DNA can show differences due to genetic alterations within the tumour genome. We applied this approach to study low-grade extranodal marginal zone B-cell lymphoma (of MALT type). After digestion with restriction enzymes, DNA samples were separately amplified by PCR with three different Alu-primers. A comparison between the fingerprint pattern from lymphoma and normal samples was made. Inter-Alu bands differing between the two samples were excised from the gel, cloned and sequenced. Nine cases of low-grade MALT-lymphomas have been analysed, giving seventeen different bands between tumour and normal. DNA sequence analysis showed identities for three of them with sequences available at the GenBank. The methodology of Alu-PCR to detect DNA-based abnormalities, in addition or combination with RNA-based methods, is a powerful tool to identify candidate regions frequently altered in tumours. With the increased available genomic sequences through the Human Genome Project, there will be an increasing probability of picking up perfect homologies with these sequences using cloned differential Alu-PCR bands in BLAST searches through genome databases.
Alu Elements↗
Prevalence of Helicobacter pylori and hepatitis C virus infections among non-Hodgkin's lymphoma patients in Southern Switzerland.
BACKGROUND AND OBJECTIVE: Several recent studies have reported a high rate of previous hepatitis C virus (HCV) infection in patients with non-Hodgkin's lymphoma (NHL). However, it appears that there are marked geographical differences in the prevalence of HCV among NHL patients. There is further controversy concerning a possible pathogenetic link between HCV and certain histologic lymphoma subtypes, in particular MALT lymphomas, and it has recently been speculated that HCV might be involved in the multistep process of gastric lymphoma genesis, in addition to the well established role of chronic Helicobacter pylori infection. The aim of this study was to investigate the prevalence of HCV and H. pylori infections in patients with B-cell NHL in Southern Switzerland. DESIGN AND METHODS: One hundred and eighty newly diagnosed HIV-negative B-cell NHL patients, consecutively seen at a referral oncology center in Southern Switzerland between 1990 and 1995 were prospectively studied. A microparticle enzyme immunoassay was used to detect antibodies to HCV. Serologic determination of HCV genotype was done by the Murex method. The quantitative detection of IgG anti-H. pylori was performed by the Biorad GAP test. RESULTS: Infection with HCV was detected in 17/180 patients (9.4%; 95% C.I., 6%-15%). This prevalence is significantly higher than that observed in a large survey of 5424 new blood donors from the same area tested in 1992-97 (0.9%; 95% C.I., 0.7-1.2). Neither histologic subtypes nor specific extranodal presentations of NHL were associated with a higher prevalence of HCV. HCV serotype 2 (corresponding to genotypes 2a-c) was the most common. HCV infection was significantly associated with a shorter progression-free survival at both univariate and multivariate analysis. Anti-Helicobacter antibodies were detected in 81/180 patients (45%; 95% C.I., 38%-53%) and H. pylori infection was significantly associated with the development of primary lymphomas of the stomach. INTERPRETATION AND CONCLUSIONS: A high prevalence of HCV infection was detected in NHL lymphoma patients and was associated with a shorter time to lymphoma progression. HCV infection was not correlated with primary gastric presentation or with MALT-type histology. Our findings further support the key role of H.pylori infection in the pathogenesis of primary gastric lymphoma of MALT-type. The possible role of HCV in the pathogenesis of NHL should be further investigated.
Aged↗
Primary extranodal non-Hodgkin's lymphomas. Part 2: Head and neck, central nervous system and other less common sites.
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Central Nervous System Neoplasms↗
Microsatellite instability in gastric MALT lymphomas and other associated neoplasms.
BACKGROUND: Microsatellite instability (MSI), caused by a reduced efficacy of the DNA mismatch repair (MMR) machinery, represents a type of genomic instability frequently detected in HNPCC spectrum cancers and in a subset of sporadic carcinomas. The involvement of MSI in the pathogenesis of gastric lymphoma of mucosa-associated lymphoid tissue (MALT) has never been conclusively investigated. In this study, we tested the presence of MSI in tumor samples of patients harboring both MALT lymphomas and other types of malignancies. MATERIALS AND METHODS: We examined 10 microsatellite loci (D3S11, D3S1261, D3S1265, D6S262, D6S193, BAT-26, BAT-25, D17S250, APC, D2S123) out of a total of 34 primary tumors from 14 patients with MALT lymphomas and one or more additional neoplasms. The patients' MSI results were also tested for an association with a positive family history of cancer. RESULTS: MSI, defined by the presence of microsatellite alterations in more than 40% of the examined loci, was scored negative in all tumors studied, and pedigree analysis failed to identify any condition of familial cancer among the patients examined. CONCLUSIONS: The present study suggests that defects in DNA mismatch repair do not contribute significantly to the molecular pathogenesis of MALT lymphomas and associated neoplasms.
Colorectal Neoplasms, Hereditary Nonpolyposis↗
Stage-modified international prognostic index effectively predicts clinical outcome of localized primary gastric diffuse large B-cell lymphoma. International Extranodal Lymphoma Study Group (IELSG)
BACKGROUND: The definition of prognostic parameters in early stages of gastric lymphoma is still controversial. The aim of this retrospective analysis was to assess the value of the stage-modified international prognostic index (IPI) in predicting the outcome of a large, consecutive series of patients with PGL of diffuse large B-cell histology (DLCL). PATIENTS AND METHODS: Three hundred twelve consecutive, newly-diagnosed, patients with localized PGL (stages I-IIE according to the 'Lugano staging system for GI lymphomas') referred from April 1972 to December 1997 to eight Italian and one Swiss centers were reviewed and their outcomes updated to June 1998. One hundred three patients were treated with single-modality therapy, while two hundred four received combined-modality treatment, most of which included surgery and short-term chemotherapy. RESULTS: After a median follow-up of 66 months (range 0.6-300 months), 195 (64%) were alive in first continuous complete remission (CCR). The five-year estimates of overall survival (OS) and event-free survival (EFS) were 75% and 67%, respectively. OS and EFS varied according to IPI, from, respectively, 90% and 82% for patients with 0-1 risk factors, to 40% and 35% for patients with > or = 3 risk factors (P = 0.00001). Cox regression analysis showed that IPI was the strongest predictor of survival. CONCLUSIONS: This study shows that stage-modified IPI is an effective predictive model in patients with primary DLCL of the stomach, enabling identification of patients with significantly different outcomes.
Adolescent↗
Variability of polymerase chain reaction detection of the bcl-2-IgH translocation in an international multicentre study.
BACKGROUND: The capacity of the polymerase chain reaction (PCR) to detect very low numbers of cells bearing a t(14;18) translocation has led to its application in assessment of the results of treatment for follicular lymphoma, and suggestions that therapy might be guided by molecular studies. To test the reliability of PCR a collaborative study was undertaken to compare results from different laboratories in Europe and North America. METHODS: Twenty laboratories with records of publication in molecular diagnostics were sent blood from normal donors with varying numbers of t(14;18)-bearing cells added from a cell line with a translocation in the major breakpoint region (MBR) of the bcl-2 gene. Samples contained 1000, 100, 10, 1 or 0 cells per ml of whole blood and were sent blinded in duplicate. PCR methodology varied widely, with the total number of amplification cycles between 30 and 70, and 13 different primers used for the MBR region. Twelve laboratories used nested PCR and eight single round amplification. RESULTS: The sensitivity of nested and single round PCR was similar at 100 cells/ml but below this the nested method proved significantly more sensitive. The false positive rate was 28%, with 11 samples from 9 laboratories reported as positive when no t(14;18) cells were added. PCR product size and sequence analysis showed that false positives were due to contamination from cell-line DNA rather than background translocations in the donors. There was no significant difference in false positive rates between nested and single round techniques. CONCLUSION: The polymerase chain reaction to detect bcl-2-IgH rearrangements is presently carried out with widely disparate results. Further effort is required to bring forward a standard PCR protocol which can be re-tested in different laboratories to improve accuracy and reproducibility. The application of quantitative techniques such as real-time PCR may resolve many of the problems presently encountered.
Adult↗
Primary mediastinal large B-cell lymphoma: the need for prospective controlled clinical trials.
Primary mediastinal large-B cell lymphomas (PMLCL) are considered to be a distinct clinicopathologic entity among the diffuse large B-cell lymphomas. This study evaluated the prognostic factors and therapeutic outcome of PMLCL in a single-institution series. Twenty seven patients were reviewed. Nineteen of the 27 had Stage I-II and 8 had Stage III-IV disease. B-symptoms were found in 11 (41%) and bulky disease in 10 (37%) patients. All were initially given combination chemotherapy (CT): doxorubicin-containing regimens to 23 patients (11 patients had CHOP, 12 received more intensive third-generation regimens) and 4 elderly (>70 years) patients received CVP. Eleven responders were consolidated with irradiation (RT) as part of their initial treatment, with a median total dose of 39 Gy. Nineteen patients (70%) achieved clinical remission (15 CR and 4 PR) with their initial therapy. Forty-four percent of patients remained progression-free and 59% are alive at 3 years. The actuarial 10-year time to progression (TTP) and overall survival (OS) were 44% and 50%, respectively. Age >60 years, performance status >1 and IPI intermediate-high to high risk were significantly associated with poorer OS and TTP by univariate analysis (log-rank test). A better outcome was associated with the use of more aggressive chemotherapy regimens or with the inclusion of RT in the first-line treatment. Our analyses suggest that the application of radiotherapy in combination regimens and the use of more aggressive chemotherapy in the treatment of this particular type of lymphoma should now be evaluated in prospective randomized trials.
Actuarial Analysis↗
ChlVPP/ABV-VP16 hybrid regimen for advanced Hodgkin's disease: a study in 36 patients.
Prolonged remission can now be induced in the majority of patients with advanced Hodgkin's disease (HD) by the use of non-cross-resistant regimens. The aim of this retrospective analysis was to evaluate the efficacy and tolerability of a hybrid chemotherapy regimen (ChlVPP/ABV-VP16) in this unfavorable subset of patients. From 1982 to 1997 thirty-six previously untreated patients with advanced HD, Stages IIB to IV according to the Ann Arbor classification, were treated with the ChlVPP/ABV-VP16 regimen. The median age of the group was 29 years (range, 18 to 74), and 50% of them had bulky disease. Complete remission (CR) was induced in 31 patients (86%); 3 patients achieved partial responses and 2 had progressive disease. The median follow-up duration is 5.7 years, with a 5-year overall survival rate of 80%. At 5 years, the time to progression (TTP) and event-free survival (EFS) were 71% and 64%, respectively. Acute toxicity was quite acceptable, and there were no treatment-related deaths. A total of 3 second malignancies (8%) were documented. In conclusion, the ChlVPP/ABV-VP16 hybrid is an active regimen for use in advanced HD. Its overall survival, TTP and CR rates make this regimen an attractive alternative to MOPP/ABVD. However, the possibility of the development of second tumors is worrisome, although the relatively brief interval between the end of treatment and tumor detection may imply caution about the possible relationship.
Adult↗
Molecular genetics of extranodal marginal zone (MALT-type) B-cell lymphoma.
Mucosa-associated lymphoid tissue lymphoma is now classified as extranodal marginal zone B-cell lymphoma. We reviewed the current literature on the biological and genetic mechanisms that lead to the development and progression of this unusual lymphoma. Particular attention was given to the clinical and biological significance of the immunoglobulin genes rearrangement, that has been proposed and widely used both diagnostically and as a tool to monitor the response to antibiotic treatment.
Amino Acid Sequence↗