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Etiology and therapy of Helicobacter pylori-associated gastric lymphomas

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Abstract

The WHO separates marginal zone B-cell lymphomas (MZBL) of nodal and extranodal type. Both arise from memory B cells of the marginal zone. Extranodal MZBL of the mucosa-associated lymphatic tissue (MALT) have characteristic features such as homing in epithelial tissue, lymphoepithelial destruction, and a very indolent clinical course. They arise in epithelial tissues normally devoid of lymphatic cells, where the lymphatic tissue was acquired after, for instance, a chronic infection. The best example here is infection of the stomach with Helicobacter pylori (Hp). Besides the classical association with gastric MALT lymphomas, there have been reports in which an association between Hp and diffuse large B-cell lymphoma (DLBCL) has been observed as well. Consequently, cure of Hp infection resulted in remission induction not only in gastric MALT lymphomas, but also in some patients with very limited stages of DLBCL of the stomach. In addition to the association with Hp, progress has been made with regard to MALT lymphoma biology. Translocation t(1;14) involving the Bcl-10 gene, and translocation t(11;18) involving a novel gene called MLT1, both result in activation of the crucial transcription factor NF-kappaB. These genetic events seem specific in that they have been observed only in MALT lymphomas. Once present, at least the more frequently observed translocation t(11;18) renders cells resistant to cure of Hp infection. Another clinically important question is that in many patients in complete remission after cure of Hp infection, detection of minimal residual disease is positive. Whether these cells are normal memory B cells (with the identical B-cell rearrangement as the original lymphoma clone), or dormant lymphoma cells, is unclear at present. In patients not responding to cure of Hp infection, several treatment options are discussed. MALT lymphomas have opened up a new discussion of lymphoma biology and have thus been called a model disease.

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References

  1. Stolte M, Bayerdorffer E, Morgner A, Alpen B, Wundisch T, Thiede C, Neubauer A (2002) Helicobacter and gastric MALT lymphoma. Gut 50:iii19–24

    PubMed  Google Scholar 

  2. Cavalli F, Isaacson PG, Gascoyne RD, Zucca E (2001) MALT lymphomas. Hematology (Am Soc Hematol Educ Program) 241–258

  3. Chan JK, Ng CS, Isaacson PG (1990) Relationship between high-grade lymphoma and low-grade B-cell mucosa-associated lymphoid tissue lymphoma (MALToma) of the stomach. Am J Pathol 136:1153–1164

    CAS  PubMed  Google Scholar 

  4. de Jong D, Boot H, van Heerde P, Hart GA, Taal BG (1997) Histological grading in gastric lymphoma: pretreatment criteria and clinical relevance. Gastroenterology 112:1466–1474

    Google Scholar 

  5. Isaacson P, Wright DH (1983) Malignant lymphoma of mucosa-associated lymphoid tissue. A distinctive type of B-cell lymphoma. Cancer 52:1410–1416

    CAS  PubMed  Google Scholar 

  6. Wyatt JI, Rathbone BJ (1988) Immune response of the gastric mucosa to Campylobacter pylori. Scand J Gastroenterol 142 [Suppl]:44–49

    Google Scholar 

  7. Stolte M, Eidt S (1989) Lymphoid follicles in antral mucosa: immune response to Campylobacter pylori? J Clin Pathol 42:1269–1271

    Google Scholar 

  8. Genta RM, Hamner HW, Graham DY (1993) Gastric lymphoid follicles in Helicobacter pylori infection: frequency, distribution, and response to triple therapy. Hum Pathol 24:577–583

    CAS  PubMed  Google Scholar 

  9. Solcia E, Villani L, Fiocca R, Luinetti O, Boldorini R, Trespi E, Perego M, Alvisi C, Lazzaroni M, Bianchi Porro G (1994) Effects of eradication of Helicobacter pylori on gastritis in duodenal ulcer patients. Scand J Gastroenterol 201 [Suppl]:28–34

    Google Scholar 

  10. Oberhuber G, Puspok A, Dejaco C, Hammer J, Zauner C, Pfeffel F, Fiedler R, Potzi R, Allerberger F, Wrba F (1996) Minimal chronic inactive gastritis: indicator of pre-existing Helicobacter pylori gastritis? Pathol Res Pract 192:1016–1021

    Google Scholar 

  11. van der Hulst RW, van der Ende A, Dekker FW, Ten Kate FJ, Weel JF, Keller JJ, Kruizinga SP, Dankert J, Tytgat GN (1997) Effect of Helicobacter pylori eradication on gastritis in relation to cagA: a prospective 1-year follow-up study. Gastroenterology 113:25–30

    Google Scholar 

  12. Chen XY, Liu WZ, Shi Y, Zhang DZ, Xiao SD, Tytgat GN (2002) Helicobacter pylori associated gastric diseases and lymphoid tissue hyperplasia in gastric antral mucosa. J Clin Pathol 55:133–137

    CAS  PubMed  Google Scholar 

  13. Doglioni C, Wotherspoon AC, Moschini A, de Boni M, Isaacson PG (1992) High incidence of primary gastric lymphoma in northeastern Italy. Lancet 339:834–835

    CAS  PubMed  Google Scholar 

  14. Cogliatti SB, Schmid U, Schumacher U, Eckert F, Hansmann ML, Hedderich J, Takahashi H, Lennert K (1991) Primary B-cell gastric lymphoma: a clinicopathological study of 145 patients. Gastroenterology 101:1159–1170

    Google Scholar 

  15. Eidt S, Stolte M, Fischer R (1994) Helicobacter pylori gastritis and primary gastric non-Hodgkin's lymphomas. J Clin Pathol 47:436–439

    CAS  PubMed  Google Scholar 

  16. Parsonnet J, Hansen S, Rodriguez L, Gelb AB, Warnke RA, Jellum E, Orentreich N, Vogelman JH, Friedman GD (1994) Helicobacter pylori infection and gastric lymphoma. N Engl J Med 330:1267–1271

    CAS  PubMed  Google Scholar 

  17. Zucca E, Bertoni F, Roggero E, Bosshard G, Cazzaniga G, Pedrinis E, Biondi A, Cavalli F (1998) Molecular analysis of the progression from Helicobacter pylori-associated chronic gastritis to mucosa-associated lymphoid-tissue lymphoma of the stomach. N Engl J Med 338:804–810

    Article  CAS  PubMed  Google Scholar 

  18. Wotherspoon AC, Doglioni C, Diss TC, Pan L, Moschini A, de Boni M, Isaacson PG (1993) Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet 342:575–577

    CAS  PubMed  Google Scholar 

  19. Bayerdorffer E, Neubauer A, Rudolph B, Thiede C, Lehn N, Eidt S, Stolte M (1995) Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. MALT Lymphoma Study Group. Lancet 345:1591–1594

    PubMed  Google Scholar 

  20. Roggero E, Zucca E, Pinotti G, Pascarella A, Capella C, Savio A, Pedrinis E, Paterlini A, Venco A, Cavalli F (1995) Eradication of Helicobacter pylori infection in primary low-grade gastric lymphoma of mucosa-associated lymphoid tissue. Ann Intern Med 122:767–769

    CAS  PubMed  Google Scholar 

  21. Weismuller J, Seifert E, Goronzy R, Stolte M (1986) Malignant lymphoma of the stomach: progress in early diagnosis (in German). Schweiz Rundsch Med Prax 75:1531–1532

    CAS  PubMed  Google Scholar 

  22. Eidt S, Stolte M (1994) Evidence of a malignant cycle in early gastric lymphoma. Endoscopy 26:299–302

    CAS  PubMed  Google Scholar 

  23. Wotherspoon AC, Doglioni C, Isaacson PG (1992) Low-grade gastric B-cell lymphoma of mucosa-associated lymphoid tissue (MALT): a multifocal disease. Histopathology 20:29–34

    CAS  PubMed  Google Scholar 

  24. Isaacson PG, Spencer J (1987) Malignant lymphoma of mucosa-associated lymphoid tissue. Histopathology 11:445–462

    CAS  PubMed  Google Scholar 

  25. Isaacson PG, Wotherspoon AC, Diss T, Pan LX (1991) Follicular colonization in B-cell lymphoma of mucosa-associated lymphoid tissue. Am J Surg Pathol 15:819–828

    CAS  PubMed  Google Scholar 

  26. Spencer J, Finn T, Pulford KA, Mason DY, Isaacson PG (1985) The human gut contains a novel population of B lymphocytes which resemble marginal zone cells. Clin Exp Immunol 62:607–612

    CAS  PubMed  Google Scholar 

  27. Sackmann M, Morgner A, Rudolph B, Neubauer A, Thiede C, Schulz H, Kraemer W, Boersch G, Rohde P, Seifert E, Stolte M, Bayerdoerffer E (1997) Regression of gastric MALT lymphoma after eradication of Helicobacter pylori is predicted by endosonographic staging. MALT Lymphoma Study Group. Gastroenterology 113:1087–1090

    CAS  PubMed  Google Scholar 

  28. Fusaroli P, Buscarini E, Peyre S, Federici T, Parente F, De Angelis C, Bonanno G, Meroni E, Napolitano V, Pisani A, Sottili S, Togliani T, Caletti G (2002) Interobserver agreement in staging gastric malt lymphoma by EUS. Gastrointest Endosc 55:662–668

    Article  PubMed  Google Scholar 

  29. Steinbach G, Ford R, Glober G, Sample D, Hagemeister FB, Lynch PM, McLaughlin PW, Rodriguez MA, Romaguera JE, Sarris AH, Younes A, Luthra R, Manning JT, Johnson CM, Lahoti S, Shen Y, Lee JE, Winn RJ, Genta RM, Graham DY, Cabanillas FF (1999) Antibiotic treatment of gastric lymphoma of mucosa-associated lymphoid tissue. An uncontrolled trial. Ann Intern Med 131:88–95

    CAS  PubMed  Google Scholar 

  30. Qin Y, Greiner A, Trunk MJ, Schmausser B, Ott MM, Muller-Hermelink HK (1995) Somatic hypermutation in low-grade mucosa-associated lymphoid tissue-type B-cell lymphoma. Blood 86:3528–3534

    CAS  PubMed  Google Scholar 

  31. Du MQ, Xu CF, Diss TC, Peng HZ, Wotherspoon AC, Isaacson PG, Pan LX (1996) Intestinal dissemination of gastric mucosa-associated lymphoid tissue lymphoma. Blood 88:4445–4451

    CAS  PubMed  Google Scholar 

  32. Du M, Diss TC, Xu C, Peng H, Isaacson PG, Pan L (1996) Ongoing mutation in MALT lymphoma immunoglobulin gene suggests that antigen stimulation plays a role in the clonal expansion. Leukemia 10:1190–1197

    CAS  PubMed  Google Scholar 

  33. Thiede C, Alpen B, Morgner A, Schmidt M, Ritter M, Ehninger G, Stolte M, Bayerdorffer E, Neubauer A (1998) Ongoing somatic mutations and clonal expansions after cure of Helicobacter pylori infection in gastric mucosa-associated lymphoid tissue B-cell lymphoma. J Clin Oncol 16:3822–3831

    CAS  PubMed  Google Scholar 

  34. Du MQ, Isaccson PG (2002) Gastric MALT lymphoma: from aetiology to treatment. Lancet Oncol 3:97–104

    Article  CAS  PubMed  Google Scholar 

  35. Hussell T, Isaacson PG, Crabtree JE, Spencer J (1993) The response of cells from low-grade B-cell gastric lymphomas of mucosa-associated lymphoid tissue to Helicobacter pylori. Lancet 342:571–574

    CAS  PubMed  Google Scholar 

  36. Hussell T, Isaacson PG, Crabtree JE, Dogan A, Spencer J (1993) Immunoglobulin specificity of low grade B cell gastrointestinal lymphoma of mucosa-associated lymphoid tissue (MALT) type. Am J Pathol 142:285–292

    CAS  PubMed  Google Scholar 

  37. Greiner A, Knorr C, Qin Y, Sebald W, Schimpl A, Banchereau J, Muller-Hermelink HK (1997) Low-grade B cell lymphomas of mucosa-associated lymphoid tissue (MALT-type) require CD40-mediated signaling and Th2-type cytokines for in vitro growth and differentiation. Am J Pathol 150:1583–1593

    CAS  PubMed  Google Scholar 

  38. D'Elios MM, Amedei A, Manghetti M, Costa F, Baldari CT, Quazi AS, Telford JL, Romagnani S, Del Prete G (1999) Impaired T-cell regulation of B-cell growth in Helicobacter pylori--related gastric low-grade MALT lymphoma. Gastroenterology 117:1105–1112

    Google Scholar 

  39. Riedel S, Kraft M, Kucharzik T, Pauels HG, Tiemann M, Steinbuchel A, Domschke W, Lugering N (2001) CD4+ Th1-cells predominate in low-grade B-cell lymphoma of gastric mucosa-associated lymphoid tissue (MALT type). Scand J Gastroenterol 36:1198–1203

    Google Scholar 

  40. Auer IA, Gascoyne RD, Connors JM, Cotter FE, Greiner TC, Sanger WG, Horsman DE (1997) t(11;18)(q21;q21) is the most common translocation in MALT lymphomas. Ann Oncol 8:979–985

    Article  CAS  PubMed  Google Scholar 

  41. Baens M, Maes B, Steyls A, Geboes K, Marynen P, De Wolf-Peeters C (2000) The product of the t(11;18), an API2-MLT fusion, marks nearly half of gastric MALT type lymphomas without large cell proliferation. Am J Pathol 156:1433–1439

    CAS  PubMed  Google Scholar 

  42. Kalla J, Stilgenbauer S, Schaffner C, Wolf S, Ott G, Greiner A, Rosenwald A, Dohner H, Muller-Hermelink HK, Lichter P (2000) Heterogeneity of the API2-MALT1 gene rearrangement in MALT-type lymphoma. Leukemia 14:1967–1974

    Article  CAS  PubMed  Google Scholar 

  43. Liu H, Ruskon-Fourmestraux A, Lavergne-Slove A, Ye H, Molina T, Bouhnik Y, Hamoudi RA, Diss TC, Dogan A, Megraud F, Rambaud JC, Du MQ, Isaacson PG (2001) Resistance of t(11;18) positive gastric mucosa-associated lymphoid tissue lymphoma to Helicobacter pylori eradication therapy. Lancet 357:39–40

    Article  CAS  PubMed  Google Scholar 

  44. Liu H, Ye H, Ruskone-Fourmestraux A, De Jong D, Pileri S, Thiede C, Lavergne A, Boot H, Caletti G, Wundisch T, Molina T, Taal BG, Elena S, Thomas T, Zinzani PL, Neubauer A, Stolte M, Hamoudi RA, Dogan A, Isaacson PG, Du MQ (2002) T(11;18) is a marker for all stage gastric MALT lymphomas that will not respond to H. pylori eradication. Gastroenterology 122:1286–1294

    Google Scholar 

  45. Motegi M, Yonezumi M, Suzuki H, Suzuki R, Hosokawa Y, Hosaka S, Kodera Y, Morishima Y, Nakamura S, Seto M (2000) API2-MALT1 chimeric transcripts involved in mucosa-associated lymphoid tissue type lymphoma predict heterogeneous products. Am J Pathol 156:807–812

    CAS  PubMed  Google Scholar 

  46. Ott G, Katzenberger T, Greiner A, Kalla J, Rosenwald A, Heinrich U, Ott MM, Muller-Hermelink HK (1997) The t(11;18)(q21;q21) chromosome translocation is a frequent and specific aberration in low-grade but not high-grade malignant non-Hodgkin's lymphomas of the mucosa-associated lymphoid tissue (MALT-) type. Cancer Res 57:3944–3948

    CAS  PubMed  Google Scholar 

  47. Dierlamm J, Baens M, Wlodarska I, Stefanova-Ouzounova M, Hernandez JM, Hossfeld DK, De Wolf-Peeters C, Hagemeijer A, Van den Berghe H, Marynen P (1999) The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21)p6ssociated with mucosa-associated lymphoid tissue lymphomas. Blood 93:3601–3609

    PubMed  Google Scholar 

  48. Akagi T, Motegi M, Tamura A, Suzuki R, Hosokawa Y, Suzuki H, Ota H, Nakamura S, Morishima Y, Taniwaki M, Seto M (1999) A novel gene, MALT1 at 18q21, is involved in t(11;18) (q21;q21) found in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue. Oncogene 18:5785–5794

    Article  CAS  PubMed  Google Scholar 

  49. Morgan JA, Yin Y, Borowsky AD, Kuo F, Nourmand N, Koontz JI, Reynolds C, Soreng L, Griffin CA, Graeme-Cook F, Harris NL, Weisenburger D, Pinkus GS, Fletcher JA, Sklar J (1999) Breakpoints of the t(11;18)(q21;q21) in mucosa-associated lymphoid tissue (MALT) lymphoma lie within or near the previously undescribed gene MALT1 in chromosome 18. Cancer Res 59:6205–6213

    CAS  PubMed  Google Scholar 

  50. Willis TG, Jadayel DM, Du MQ, Peng H, Perry AR, Abdul-Rauf M, Price H, Karran L, Majekodunmi O, Wlodarska I, Pan L, Crook T, Hamoudi R, Isaacson PG, Dyer MJ (1999) Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types. Cell 96:35–45

    CAS  PubMed  Google Scholar 

  51. Zhang Q, Siebert R, Yan M, Hinzmann B, Cui X, Xue L, Rakestraw KM, Naeve CW, Beckmann G, Weisenburger DD, Sanger WG, Nowotny H, Vesely M, Callet-Bauchu E, Salles G, Dixit VM, Rosenthal A, Schlegelberger B, Morris SW (1999) Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32). Nat Genet 22:63–68

    CAS  Google Scholar 

  52. Lucas PC, Yonezumi M, Inohara N, McAllister-Lucas LM, Abazeed ME, Chen FF, Yamaoka S, Seto M, Nunez G (2001) Bcl10 and MALT1, independent targets of chromosomal translocation in malt lymphoma, cooperate in a novel NF-kappa B signaling pathway. J Biol Chem 276:19012–19019

    Article  CAS  PubMed  Google Scholar 

  53. Du MQ, Peng H, Liu H, Hamoudi RA, Diss TC, Willis TG, Ye H, Dogan A, Wotherspoon AC, Dyer MJ, Isaacson PG (2000) BCL10 gene mutation in lymphoma. Blood 95:3885–3890

    CAS  PubMed  Google Scholar 

  54. Maes B, Demunter A, Peeters B, De Wolf-Peeters C (2002) BCL10 mutation does not represent an important pathogenic mechanism in gastric MALT-type lymphoma, and the presence of the API2-MLT fusion is associated with aberrant nuclear BCL10 expression. Blood 99:1398–1404

    Article  CAS  PubMed  Google Scholar 

  55. Ye H, Dogan A, Karran L, Willis TG, Chen L, Wlodarska I, Dyer MJ, Isaacson PG, Du MQ (2000) BCL10 expression in normal and neoplastic lymphoid tissue. Nuclear localization in MALT lymphoma. Am J Pathol 157:1147–1154

    CAS  PubMed  Google Scholar 

  56. Uren AG, O'Rourke K, Aravind LA, Pisabarro MT, Seshagiri S, Koonin EV, Dixit VM (2000) Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma. Mol Cell 6:961–967

    CAS  Google Scholar 

  57. Liu H, Ye H, Dogan A, Ranaldi R, Hamoudi RA, Bearzi I, Isaacson PG, Du MQ (2001) T(11;18)(q21;q21) is associated with advanced mucosa-associated lymphoid tissue lymphoma that expresses nuclear BCL10. Blood 98:1182–1187

    Article  CAS  PubMed  Google Scholar 

  58. Alpen B, Neubauer A, Dierlamm J, Marynen P, Thiede C, Bayerdorfer E, Stolte M (2000) Translocation t(11;18) absent in early gastric marginal zone B-cell lymphoma of MALT type responding to eradication of Helicobacter pylori infection. Blood 95:4014–4015

    CAS  PubMed  Google Scholar 

  59. Nakamura T, Nakamura S, Yonezumi M, Suzuki T, Matsuura A, Yatabe Y, Yokoi T, Ohashi K, Seto M (2000) Helicobacter pylori and the t(11;18)(q21;q21) translocation in gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type. Jpn J Cancer Res 91:301–309

    CAS  PubMed  Google Scholar 

  60. Remstein ED, Kurtin PJ, James CD, Wang XY, Meyer RG, Dewald GW (2002) Mucosa-associated lymphoid tissue lymphomas with t(11;18)(q21;q21) and mucosa-associated lymphoid tissue lymphomas with aneuploidy develop along different pathogenetic pathways. Am J Pathol 161:63–71

    PubMed  Google Scholar 

  61. Starostik P, Patzner J, Greiner A, Schwarz S, Kalla J, Ott G, Muller-Hermelink HK (2002) Gastric marginal zone B-cell lymphomas of MALT type develop along 2 distinct pathogenetic pathways. Blood 99:3–9

    Article  CAS  PubMed  Google Scholar 

  62. Barth TF, Bentz M, Leithauser F, Stilgenbauer S, Siebert R, Schlotter M, Schlenk RF, Dohner H, Moller P (2002) Pathogenic complexity of gastric B-cell lymphoma. Blood 100:1095–1096, discussion 1096–1097

    Article  CAS  PubMed  Google Scholar 

  63. Streubel B, Lamprecht A, Dierlamm J, Cerroni L, Stolte M, Ott G, Raderer M, Chott A (2003) T(14;18)(q32;q21) involving IGH and MALT1 is a frequent chromosomal aberration in MALT lymphoma. Blood 101:2335–2339

    Article  CAS  PubMed  Google Scholar 

  64. Du M, Peng H, Singh N, Isaacson PG, Pan L (1995) The accumulation of p53 abnormalities is associated with progression of mucosa-associated lymphoid tissue lymphoma. Blood 86:4587–4593

    CAS  PubMed  Google Scholar 

  65. Dierlamm J, Pittaluga S, Wlodarska I, Stul M, Thomas J, Boogaerts M, Michaux L, Driessen A, Mecucci C, Cassiman JJ, et al. (1996) Marginal zone B-cell lymphomas of different sites share similar cytogenetic and morphologic features. Blood 87:299–307

    CAS  PubMed  Google Scholar 

  66. de Wolf-Peeters C, Pittaluga S, Dierlamm J, Wlodarska I, Van Den Berghe H (1997) Marginal zone B-cell lymphomas including mucosa-associated lymphoid tissue type lymphoma (MALT), monocytoid B-cell lymphoma and splenic marginal zone cell lymphoma and their relation to the reactive marginal zone. Leuk Lymphoma 26:467–478

    PubMed  Google Scholar 

  67. Peng H, Diss T, Isaacson PG, Pan L (1997) c-myc gene abnormalities in mucosa-associated lymphoid tissue (MALT) lymphomas. J Pathol 181:381–386

    Article  CAS  PubMed  Google Scholar 

  68. Martinez-Delgado B, Fernandez-Piqueras J, Garcia MJ, Arranz E, Gallego J, Rivas C, Robledo M, Benitez J (1997) Hypermethylation of a 5' CpG island of p16 is a frequent event in non-Hodgkin's lymphoma. Leukemia 11:425–428

    Article  CAS  PubMed  Google Scholar 

  69. Gronbaek K, Straten PT, Ralfkiaer E, Ahrenkiel V, Andersen MK, Hansen NE, Zeuthen J, Hou-Jensen K, Guldberg P (1998) Somatic Fas mutations in non-Hodgkin's lymphoma: association with extranodal disease and autoimmunity. Blood 92:3018–3024

    PubMed  Google Scholar 

  70. Martinez-Delgado B, Robledo M, Arranz E, Osorio A, Garcia MJ, Echezarreta G, Rivas C, Benitez J (1998) Hypermethylation of p15/ink4b/MTS2 gene is differentially implicated among non-Hodgkin's lymphomas. Leukemia 12:937–941

    Article  CAS  PubMed  Google Scholar 

  71. Ohashi S, Segawa K, Okamura S, Urano H, Kanamori S, Ishikawa H, Hara K, Hukutomi A, Shirai K, Maeda M (2000) A clinicopathologic study of gastric mucosa-associated lymphoid tissue lymphoma. Cancer 88:2210–2219

    Article  CAS  PubMed  Google Scholar 

  72. Wan JH, Sykes PJ, Orell SR, Morley AA (1992) Rapid method for detecting monoclonality in B cell lymphoma in lymph node aspirates using the polymerase chain reaction. J Clin Pathol 45:420–423

    CAS  PubMed  Google Scholar 

  73. Algara P, Martinez P, Sanchez L, Villuendas R, Benitez J, Rivas C, Piris MA (1993) The detection of B-cell monoclonal populations by polymerase chain reaction: accuracy of approach and application in gastric endoscopic biopsy specimens. Hum Pathol 24:1184–1188

    CAS  PubMed  Google Scholar 

  74. Ling FC, Clarke CE, Corbett WE, Lillicrap DP (1993) Sensitivity of PCR in detecting monoclonal B cell proliferations. J Clin Pathol 46:624–627

    CAS  PubMed  Google Scholar 

  75. Diss TC, Pan L, Peng H, Wotherspoon AC, Isaacson PG (1994) Sources of DNA for detecting B cell monoclonality using PCR. J Clin Pathol 47:493–496

    CAS  PubMed  Google Scholar 

  76. De Re V, De Vita S, Carbone A, Ferraccioli G, Gloghini A, Marzotto A, Pivetta B, Dolcetti R, Boiocchi M (1995) The relevance of VDJ PCR protocols in detecting B-cell clonal expansion in lymphomas and other lymphoproliferative disorders. Tumori 81:405–409

    PubMed  Google Scholar 

  77. Lozano MD, Tierens A, Greiner TC, Wickert RS, Weisenburger DD, Chan WC (1996) Clonality analysis of B-lymphoid proliferations using the polymerase chain reaction. Cancer 77:1349–1355

    Article  CAS  PubMed  Google Scholar 

  78. Bertoni F, Cazzaniga G, Bosshard G, Roggero E, Barbazza R, De Boni M, Capella C, Pedrinis E, Cavalli F, Biondi A, Zucca E (1997) Immunoglobulin heavy chain diversity genes rearrangement pattern indicates that MALT-type gastric lymphoma B cells have undergone an antigen selection process. Br J Haematol 97:830–836

    CAS  PubMed  Google Scholar 

  79. Miklos JA, Swerdlow SH, Bahler DW (2000) Salivary gland mucosa-associated lymphoid tissue lymphoma immunoglobulin V(H) genes show frequent use of V1–69 with distinctive CDR3 features. Blood 95:3878–3884

    CAS  PubMed  Google Scholar 

  80. Aiello A, Giardini R, Tondini C, Balzarotti M, Diss T, Peng H, Delia D, Pilotti S (1999) PCR-based clonality analysis: a reliable method for the diagnosis and follow-up monitoring of conservatively treated gastric B-cell MALT lymphomas? Histopathology 34:326–330

    Google Scholar 

  81. Bertoni F, Conconi A, Capella C, Motta T, Giardini R, Ponzoni M, Pedrinis E, Novero D, Rinaldi P, Cazzaniga G, Biondi A, Wotherspoon A, Hancock BW, Smith P, Souhami R, Cotter FE, Cavalli F, Zucca E (2002) Molecular follow-up in gastric mucosa-associated lymphoid tissue lymphomas: early analysis of the LY03 cooperative trial. Blood 99:2541–2544

    Article  CAS  PubMed  Google Scholar 

  82. Montalban C, Santon A, Boixeda D, Redondo C, Alvarez I, Calleja JL, de Argila CM, Bellas C (2001) Treatment of low grade gastric mucosa-associated lymphoid tissue lymphoma in stage I with Helicobacter pylori eradication. Long-term results after sequential histologic and molecular follow-up. Haematologica 86:609–617

    CAS  PubMed  Google Scholar 

  83. Neubauer A, Thiede C, Morgner A, Alpen B, Ritter M, Neubauer B, Wundisch T, Ehninger G, Stolte M, Bayerdorffer E (1997) Cure of Helicobacter pylori infection and duration of remission of low-grade gastric mucosa-associated lymphoid tissue lymphoma. J Natl Cancer Inst 89:1350–1335

    CAS  PubMed  Google Scholar 

  84. Thiede C, Wundisch T, Neubauer B, Alpen B, Morgner A, Ritter M, Ehninger G, Stolte M, Bayerdorffer E, Neubauer A (2000) Eradication of Helicobacter pylori and stability of remissions in low-grade gastric B-cell lymphomas of the mucosa-associated lymphoid tissue: results of an ongoing multicenter trial. Recent Results Cancer Res 156:125–133

    CAS  PubMed  Google Scholar 

  85. Savio A, Franzin G, Wotherspoon AC, Zamboni G, Negrini R, Buffoli F, Diss TC, Pan L, Isaacson PG (1996) Diagnosis and posttreatment follow-up of Helicobacter pylori-positive gastric lymphoma of mucosa-associated lymphoid tissue: histology, polymerase chain reaction, or both? Blood 87:1255–1260

    Google Scholar 

  86. Calvert RJ, Evans PA, Randerson JA, Jack AS, Morgan GJ, Dixon MF (1996) The significance of B-cell clonality in gastric lymphoid infiltrates. J Pathol 180:26–32

    Article  CAS  PubMed  Google Scholar 

  87. Sorrentino D, Ferraccioli GF, DeVita S, Avellini C, Beltrami CA, Labombarda A, Bernardis V, De Biase F, Trevisi A, Pivetta B, Boiocchi M, Bartoli E (1996) B-cell clonality and infection with Helicobacter pylori: implications for development of gastric lymphoma. Gut 38:837–840

    CAS  PubMed  Google Scholar 

  88. Ferraccioli GF, Sorrentino D, De Vita S, Casatta L, Labombarda A, Avellini C, Dolcetti R, Di Luca D, Beltrami CA, Boiocchi M, Bartoli E (1996) B cell clonality in gastric lymphoid tissues of patients with Sjogren's syndrome. Ann Rheum Dis 55:311–316

    CAS  PubMed  Google Scholar 

  89. Hsi ED, Greenson JK, Singleton TP, Siddiqui J, Schnitzer B, Ross CW (1996) Detection of immunoglobulin heavy chain gene rearrangement by polymerase chain reaction in chronic active gastritis associated with Helicobacter pylori. Hum Pathol 27:290–296

    CAS  PubMed  Google Scholar 

  90. Rudolph B, Bayerdorffer E, Ritter M, Muller S, Thiede C, Neubauer B, Lehn N, Seifert E, Otto P, Hatz R, Stolte M, Neubauer A (1997) Is the polymerase chain reaction or cure of Helicobacter pylori infection of help in the differential diagnosis of early gastric mucosa-associated lymphatic tissue lymphoma? J Clin Oncol 15:1104–1109

    Google Scholar 

  91. de Mascarel A, Dubus P, Belleannee G, Megraud F, Merlio JP (1998) Low prevalence of monoclonal B cells in Helicobacter pylori gastritis patients with duodenal ulcer. Hum Pathol 29:784–790

    PubMed  Google Scholar 

  92. Torlakovic E, Cherwitz DL, Jessurun J, Scholes J, McGlennen R (1997) B-cell gene rearrangement in benign and malignant lymphoid proliferations of mucosa-associated lymphoid tissue and lymph nodes. Hum Pathol 28:166–173

    CAS  PubMed  Google Scholar 

  93. El-Zimaity HM, El-Zaatari FA, Dore MP, Oweiss S, Gutierrez O, Yuksul M, Ramchatesingh J, Graham DY (1999) The differential diagnosis of early gastric mucosa-associated lymphoma: polymerase chain reaction and paraffin section immunophenotyping. Mod Pathol 12:885–893

    CAS  PubMed  Google Scholar 

  94. Saxena A, Moshynska O, Kanthan R, Bhutani M, Maksymiuk AW, Lukie BE (2000) Distinct B-cell clonal bands in Helicobacter pylori gastritis with lymphoid hyperplasia. J Pathol 190:47–54

    Article  CAS  PubMed  Google Scholar 

  95. Hiyama T, Haruma K, Kitadai Y, Miyamoto M, Tanaka S, Yoshihara M, Sumii K, Shimamoto F, Kajiyama G (2001) B-cell monoclonality in Helicobacter pylori-associated chronic atrophic gastritis. Virchows Arch 438:232–237

    CAS  PubMed  Google Scholar 

  96. Ludwig CU, Gencik M, Shipman R (1993) Multistep transformation in low-grade lymphoproliferative diseases. Ann Oncol 4:825–830

    CAS  PubMed  Google Scholar 

  97. Thiede C, Wundisch T, Alpen B, Neubauer B, Morgner A, Schmitz M, Ehninger G, Stolte M, Bayerdorffer E, Neubauer A (2001) Long-term persistence of monoclonal B cells after cure of Helicobacter pylori infection and complete histologic remission in gastric mucosa-associated lymphoid tissue B-cell lymphoma. J Clin Oncol 19:1600–1609

    CAS  PubMed  Google Scholar 

  98. Alpen B, Thiede C, Wundisch T, Bayerdorffer E, Stolte M, Neubauer A (2001) Molecular diagnostics in low-grade gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type after Helicobacter pylori eradication therapy. Clin Lymphoma 2:103–108

    CAS  PubMed  Google Scholar 

  99. Au WY, Gascoyne RD, Le N, Viswanatha DS, Klasa RJ, Gallagher R, Connors JM (1999) Incidence of second neoplasms in patients with MALT lymphoma: no increase in risk above the background population. Ann Oncol 10:317–321

    Article  CAS  PubMed  Google Scholar 

  100. Montalban C, Castrillo JM, Lopez-Abente G, Abraira V, Serrano M, Bellas C, Piris MA, Carrion R, Cruz MA, Garcia-Larana J, Menarguez J, Rivas C (1999) Other cancers in patients with gastric MALT lymphoma. Leuk Lymphoma 33:161–168

    CAS  PubMed  Google Scholar 

  101. Zucca E, Pinotti G, Roggero E, Comi MA, Pascarella A, Capella C, Pedrinis E, Cavalli F (1995) High incidence of other neoplasms in patients with low-grade gastric MALT lymphoma. Ann Oncol 6:726–728

    CAS  PubMed  Google Scholar 

  102. Morgner A, Miehlke S, Stolte M, Neubauer A, Alpen B, Thiede C, Klann H, Hierlmeier FX, Ell C, Ehninger G, Bayerdorffer E (2001) Development of early gastric cancer 4 and 5 years after complete remission of Helicobacter pylori associated gastric low grade marginal zone B cell lymphoma of MALT type. World J Gastroenterol 7:248–253

    Google Scholar 

  103. Rosen CB, van Heerden JA, Martin JK, Jr., Wold LE, Ilstrup DM (1987) Is an aggressive surgical approach to the patient with gastric lymphoma warranted? Ann Surg 205:634–640

    Google Scholar 

  104. Schechter NR, Yahalom J (2000) Low-grade MALT lymphoma of the stomach: a review of treatment options. Int J Radiat Oncol Biol Phys 46:1093–1103

    Google Scholar 

  105. Gobbi PG, Dionigi P, Barbieri F, Corbella F, Bertoloni D, Grignani G, Jemos V, Pieresca C, Ascari E (1990) The role of surgery in the multimodal treatment of primary gastric non-Hodgkin's lymphomas. A report of 76 cases and review of the literature. Cancer 65:2528–2536

    CAS  PubMed  Google Scholar 

  106. Koch P, del Valle F, Berdel WE, Willich NA, Reers B, Hiddemann W, Grothaus-Pinke B, Reinartz G, Brockmann J, Temmesfeld A, Schmitz R, Rube C, Probst A, Jaenke G, Bodenstein H, Junker A, Pott C, Schultze J, Heinecke A, Parwaresch R, Tiemann M (2001) Primary gastrointestinal non-Hodgkin's lymphoma: II. Combined surgical and conservative or conservative management only in localized gastric lymphoma—results of the prospective German Multicenter Study GIT NHL 01/92. J Clin Oncol 19:3874–3883

    CAS  PubMed  Google Scholar 

  107. Bartlett DL, Karpeh MS, Jr., Filippa DA, Brennan MF (1996) Long-term follow-up after curative surgery for early gastric lymphoma. Ann Surg 223:53–62

    Article  CAS  PubMed  Google Scholar 

  108. Rodriguez-Sanjuan JC, Alvarez-Canas C, Casado F, Garcia-Castrillo L, Casanova D, Val-Bernal F, Naranjo A (1999) Results and prognostic factors in stage I(E)-II(E) primary gastric lymphoma after gastrectomy. J Am Coll Surg 188:296–303

    Article  CAS  PubMed  Google Scholar 

  109. Mafune KI, Tanaka Y, Suda Y, Izumo T (2001) Outcome of patients with non-Hodgkin's lymphoma of the stomach after gastrectomy: clinicopathologic study and reclassification according to the revised European-American lymphoma classification. Gastric Cancer 4:137–143

    CAS  PubMed  Google Scholar 

  110. Schechter NR, Portlock CS, Yahalom J (1998) Treatment of mucosa-associated lymphoid tissue lymphoma of the stomach with radiation alone. J Clin Oncol 16:1916–1921

    CAS  PubMed  Google Scholar 

  111. Yahalom J (2001) MALT lymphomas: a radiation oncology viewpoint. Ann Hematol 80 [Suppl 3]:B100–B105

    Google Scholar 

  112. Hammel P, Haioun C, Chaumette MT, Gaulard P, Divine M, Reyes F, Delchier JC (1995) Efficacy of single-agent chemotherapy in low-grade B-cell mucosa-associated lymphoid tissue lymphoma with prominent gastric expression. J Clin Oncol 13:2524–2529

    CAS  PubMed  Google Scholar 

  113. Jager G, Neumeister P, Brezinschek R, Hinterleitner T, Fiebiger W, Penz M, Neumann HJ, Mlineritsch B, DeSantis M, Quehenberger F, Chott A, Beham-Schmid C, Hofler G, Linkesch W, Raderer M (2002) Treatment of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type with cladribine: a phase II study. J Clin Oncol 20:3872–3877

    Article  PubMed  Google Scholar 

  114. Conconi A, Thieblemont C, Martinelli G, Ferreri AJ, Devizzi L, Peccatori F, Dell'Oro S, Filipazzi V, Dietrich PY, Gianni MA, Coiffier B, Cavalli F, Zucca E (2002) IELSG phase II study of rituximab in MALT lymphoma: final results. ASCO Meeting, Orlando, FL

    Google Scholar 

  115. Fischbach W, Goebeler-Kolve M, Starostik P, Greiner A, Muller-Hermelink HK (2002) Minimal residual low-grade gastric MALT-type lymphoma after eradication of Helicobacter pylori. Lancet 360:547–548

    Article  PubMed  Google Scholar 

  116. Peng H, Du M, Diss TC, Isaacson PG, Pan L (1997) Genetic evidence for a clonal link between low and high-grade components in gastric MALT B-cell lymphoma. Histopathology 30:425–429

    CAS  PubMed  Google Scholar 

  117. Neumeister P, Hoefler G, Beham-Schmid C, Schmidt H, Apfelbeck U, Schaider H, Linkesch W, Sill H (1997) Deletion analysis of the p16 tumor suppressor gene in gastrointestinal mucosa-associated lymphoid tissue lymphomas. Gastroenterology 112:1871–1875

    CAS  PubMed  Google Scholar 

  118. Peng H, Chen G, Du M, Singh N, Isaacson PG, Pan L (1996) Replication error phenotype and p53 gene mutation in lymphomas of mucosa-associated lymphoid tissue. Am J Pathol 148:643–648

    CAS  PubMed  Google Scholar 

  119. Sonoki T, Harder L, Horsman DE, Karran L, Taniguchi I, Willis TG, Gesk S, Steinemann D, Zucca E, Schlegelberger B, Sole F, Mungall AJ, Gascoyne RD, Siebert R, Dyer MJ (2001) Cyclin D3 is a target gene of t(6;14)(p21.1;q32.3) of mature B-cell malignancies. Blood 98:2837–2844

    Article  CAS  PubMed  Google Scholar 

  120. Chen LT, Lin JT, Shyu RY, Jan CM, Chen CL, Chiang IP, Liu SM, Su IJ, Cheng AL (2001) Prospective study of Helicobacter pylori eradication therapy in stage I(E) high-grade mucosa-associated lymphoid tissue lymphoma of the stomach. J Clin Oncol 19:4245–4251

    CAS  PubMed  Google Scholar 

  121. Alpen B, Robbecke J, Wundisch T, Stolte M, Neubauer A (2001) Helicobacter pylori eradication therapy in gastric high grade non Hodgkin's lymphoma (NHL). Ann Hematol 80 [Suppl 3]:B106–B107

  122. Gretschel S, Hunerbein M, Foss HD, Krause M, Schlag PM (2001) Regression of high-grade gastric B-cell lymphoma after eradication of Helicobacter pylori. Endoscopy 33:805–807

    Article  CAS  PubMed  Google Scholar 

  123. Salam I, Durai D, Murphy JK, Sundaram B (2001) Regression of primary high-grade gastric B-cell lymphoma following Helicobacter pylori eradication. Eur J Gastroenterol Hepatol 13:1375–1378

    Google Scholar 

  124. Morgner A, Miehlke S, Fischbach W, Schmitt W, Muller-Hermelink H, Greiner A, Thiede C, Schetelig J, Neubauer A, Stolte M, Ehninger G, Bayerdorffer E (2001) Complete remission of primary high-grade B-cell gastric lymphoma after cure of Helicobacter pylori infection. J Clin Oncol 19:2041–2048

    CAS  PubMed  Google Scholar 

  125. Hiyama T, Haruma K, Kitadai Y, Ito M, Masuda H, Miyamoto M, Tanaka S, Yoshihara M, Sumii K, Shimamoto F, Chayama K (2001) Helicobacter pylori eradication therapy for high-grade mucosa-associated lymphoid tissue lymphomas of the stomach with analysis of p53 and K-ras alteration and microsatellite instability. Int J Oncol 18:1207–1212

    Google Scholar 

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Correspondence to A. Neubauer.

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This work was kindly supported by Deutsche Krebshilfe Bonn (70.2251) and the Wilhelm Sander Stiftung

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Wündisch, T., Kim, T.D., Thiede, C. et al. Etiology and therapy of Helicobacter pylori-associated gastric lymphomas. Ann Hematol 82, 535–545 (2003). https://doi.org/10.1007/s00277-003-0677-2

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