Skip to main content
SpringerLink
Log in

Specificity of Polymerase Chain Reaction Monoclonality for Diagnosis of Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma (Direct Comparison to Southern Blot Gene Rearrangement)

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

The specificity of polymerase chain reactionmonoclonality in the diagnosis of gastric lymphoma wasprospectively evaluated. Gastric mucosal tissue fromnormal gastric mucosa (N = 13), benign gastric ulcers (N = 3), chronic Helicobacter pylori gastritis(N = 3), gastric mucosa-associated lymphoid tissue (N =16), and gastric lymphoma (N = 15) was obtained.Polymerase chain reaction amplification of theheavy-chain framework 2A gene was performed. Thesensitivity and specificity of heavy-chain clonality, inthe detection of gastric lymphoma, were 73.3% and 45.7%,respectively. Determination of monoclonality bypolymerase chain reaction methodology is not an acceptabletechnique for confirming the diagnosis of gastriclymphoma as it is too sensitive, detecting minutepopulations of clonal lymphocytes that occur in benign diseases as well as larger populations ofclonal lymphocytes associated with malignant gastriclymphoproliferative diseases. Southern blot generearrangement testing should be utilized to determineclonality in the evaluation of gastric lymphocyticinfiltrates.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

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

    Google Scholar 

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

    Google Scholar 

  3. Bayerdorfer E, Neubauer A, Rudolph B, Theide C, Lehn N, Eidt S, Stolte M, for Malt Lymphoma Study Group. Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pyloriinfection. Lancet 345:1591–1594, 1995

    Google Scholar 

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

    Google Scholar 

  5. Yardley JH, Hendrix TR: Gastritis, duodenitis, and associated ulcerative lesions. InTextbook of Gastroenterology. T Yamada, DH Alpers, C Owyang, DW Powell, FE Silverstein (eds). Philadelphia, JB Lippincott, 1995, pp 1456–1493

    Google Scholar 

  6. Isaacson PG, Norton AJ: Extranodal Lymphomas. New York, Churchill Livingstone, 1994

    Google Scholar 

  7. Zukerberg LR, Ferry JA, Southern JF, Harns NL: Lymphoid infiltrates of the stomach. Evaluation of histologic criteria for the diagnosis of low-grade gastric lymphoma on endoscopic biopsy specimens. Am J Surg Pathol 14:1087–1099, 1990

    Google Scholar 

  8. Isaacson PG: Gastrointestinal lymphomas and lymphoid hyperplasia. InNeoplastic Hematopathology. DM Knowles (ed). Baltimore, Williams and Wilkins, 1992, pp 953–978

    Google Scholar 

  9. Isaacson PG: Gastrointestinal lymphoma. Hum Pathol 25:1020–1029, 1994

    Google Scholar 

  10. Cleary ML, Chao J, Warnke R, Sklar J: Immunoglobulin gene rearrangement as a diagnostic criterion of B-cell lymphoma. Proc Natl Acad Sci USA 81:593–597, 1984

    Google Scholar 

  11. Cossman J, Zehnbauer B, Garrett CT, Smith LJ, Williams M, Jaffe ES, Hanson LO, Love J: Gene rearrangements in the diagnosis of lymphoma/leukemia. Guidelines for the use based on a multiinstitutional study. Am J Clin Pathol 95:347–354, 1991

    Google Scholar 

  12. Cossman J, Uppenkamp M, Sundeen J, Coupland R, Raffeld M: Molecular genetics and the diagnosis of lymphoma. Arch Pathol Lab Med 112:117–127, 1988

    Google Scholar 

  13. Pittaluga S, Uppenkamp M, Cossman J: Development of T3/T cell receptor gene expression in human pre-T neoplasms. Blood 69:1062–1067, 1987

    Google Scholar 

  14. Petterson V, Sambrook J: Amount of viral DNA in the genome of cells transformed by adenovirus type 2. J Mol Biol 73:125–130, 1973

    Google Scholar 

  15. Sambrook J, Fritsch EF, Maniatis T: Molecular Cloning. Cold Spring Harbor, New York, Cold Spring Harbor Laboratory Press, 1989

    Google Scholar 

  16. Banerjee SK, Makdisi WF, Weston AP, Campbell DR: Microwave-based DNA extraction from paraffin-embedded tissue for PCR amplification. Bio Techniques 18:768–770, 772–773, 1995

    Google Scholar 

  17. Davis LG, Dibner MD. Battey JF: Basic Methods in Molecular Biology. New York, Elsevier Science Publishing, 1986

    Google Scholar 

  18. Banerjee SK, Makdisi WF, Weston AP, Campbell DR: A two-step PCR technique enhances sensitivity for detecting K-rasmutations in pancreatic adenocarcinoma. Pancreas 15:16–24, 1997

    Google Scholar 

  19. Miller CW, Simon K, Aslo A, Kok K, Yokota J, Buys CH, Terada M, Koeffler HP: p53mutations in human ling tumors. Cancer Res 52:1695–1698, 1992

    Google Scholar 

  20. Kwok S, Higuchi R: Avoiding false positives with PCR. Nature 339:237–238, 1989

    Google Scholar 

  21. Ramasamy I, Brisco M, Morley A: Improved PCR method for detecting monoclonal immunoglobulin heavy chain re arrange-ment in B cell neoplasms. J Clin Pathol 45:770775, 1992

    Google Scholar 

  22. Diss TC, Peng H, Wotherspoon AC, Isaacson PG, Pan L: Detection of monoclonality in low-grade B-cell lymphomas using the polymerase chain reaction is dependent upon primer selection and lymphoma type. J Pathol 169:291–295, 1993

    Google Scholar 

  23. Achille A, Scarpa A, Montresor M, Scardoni M, Zamboni G, Chilosi M, Capelli P, Franzin G, Menestrina F: Routine application of polymerase chain reaction in the diagnosis of monoclonality of B-cell lymphoid proliferations. Diagn Mol Pathol 4:1424, 1995

    Google Scholar 

  24. Kabat EA: Sequence s of Proteins of Immunological Interest, 5th ed. Bethesda, NIH Publications, 1991

    Google Scholar 

  25. Trainor KJ, Brisco MJ, Story CJ, Morley AA: Monoclonality in B-lymphoproliferative disorders detected at the DNA level. Blood 75:2220–2222, 1990

    Google Scholar 

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

    Google Scholar 

  27. Sukpanichnant S, Vnencak-Jones CL, McCurley TL: Determination of B-cellclonality in paraffin-embedded endoscopic biopsy specimens of abnormal lymphocytic infiltrates and gastrointestinal lymphoma by polymerase chain reaction. Am J Clin Pathol 102:299–305, 1994

    Google Scholar 

  28. Inagaki H, Nonaka M, Nagaya S, Tateyama H, Sasaki M, Eimoto T: Monoclonality in gastric lymphoma detected in formalin-fixed, paraffin-embedded endoscopic biopsy specimens using immunohistochemistry, in situhybridization, and polymerase chain reaction. Diagn Mol Pathol 4:32–38, 1995

    Google Scholar 

  29. Reed TJ, Reid A, Wallberg K, O'Leary TJ, Frizzera G: Determination of B-cell clonality in paraffin-embedded lymph nodes using the polymerase chain reaction. Diagn Mol Pathol 2:42–49, 1993

    Google Scholar 

  30. Osborne BM, Pugh WC: Practicality of molecular studies to evaluate small lymphocytic proliferations in endoscopic gastric biopsies. Am J Surg Pathol 16:838–844, 1992

    Google Scholar 

  31. Mies C: Molecular pathology of paraffin-embedded tissue. Current clinical application. Diagn Mol Pathol 1:206–211, 1992

    Google Scholar 

  32. Griesser H: Applied molecular genetics in the diagnosis of malignant non-Hodgkin's lymphoma. Diagn Mol Pathol 2:177–191, 1993

    Google Scholar 

  33. Sklar J: Antigen receptor genes: Structure, function, and techniques for analysis of their rearrangements. InNeoplastic Hematopathology. DM Knowles (ed). Baltimore, Williams & Wilkins, 1992, pp 215–244

    Google Scholar 

  34. Ratech H, Masih A: Sensitive detection of clonal antigen receptor gene rearrangements in non-Hodgkin's malignant lymphoma with an anchored polymerase chain reaction-based strategy. Am J Clin Pathol 100:527–533, 1993

    Google Scholar 

  35. Sioutos N, Bagg A, Michaud GY, Irving SG, Hartmann DP, Siragy H, Oliveri DR, Locker J, Cossman J: Polymerase chain reaction versus southern blot hybridization. Detection of immunoglobulin heavy-chain gene rearrangements. Diagn Mol Pathol 4:8–13, 1995

    Google Scholar 

  36. Yokota S, Hansen-Hagge TE, Ludwig WD, Reiter A, Raghavachar A, Kleihauer E, Bartram CR: Use of polymerase chain reactions to monitor minimal residual disease in acute lymphoblastic leukemia patients. Blood 77:331–339, 1991

    Google Scholar 

  37. Gribben JG, Freedman AS, Woo SD, Blake K, Shu RS, Free-man G, Longtine JA, Pinkus GS, Nadler LM: All advanced stage non-Hodgkin's lymphomas with a polymerase chain re-action amplifiable breakpoint of bcl-2 have residual cells containing the bcl-2 rearrangement at evaluation and after treatment. Blood 78:3275–3280, 1991

    Google Scholar 

  38. Sigal SH, Saul SH, Auerbach HE, Raffensperger E, Kant JA, Brooks JJ: Gastric small lymphocytic proliferation with immunoglobulin gene rearrangement in pseudolymphoma versus lymphoma. Gastroenterology 97:195–201, 1989

    Google Scholar 

  39. Eimoto T, Futami K, Naito H, Takeshita M, Kikuchi M. Gastric pseudolymphoma with monotypic cytoplasmic immunoglobulin. Cancer 55:788793, 1985

    Google Scholar 

  40. Galton DA, Catovsky DW, Wiltshaw E: Clinical Spectrum of lymphoproliferative diseases. Cancer 42:901–910, 1978

    Google Scholar 

  41. Wood GS, Weiss LM, Hu CH, Abel EA, Hoppe RT, Warnke RA, Sklar J: T-cell antigen deficiencies and clonal rearrange-ments of T-cell receptor genes in pagetoid reticulosis (Woringer-Kolopp disease ). N Engl J Med 318:164–167, 1988

    Google Scholar 

  42. LeBoit PE, Abel EA, Cleary ML, Hoppe RT, Williams ML, Wood GS, Parslow TG: Clonal rearrangement of the T-cell receptor beta gene in the circulating lymphocytes of erythrodermic follicular mucinosis. Blood 71:1329–1333, 1988

    Google Scholar 

  43. Jaworsky C, Cirillo-Hyland V, Petrozzi JW, Lessin SR, Murphy GF: Regressing atypical histiocytosis: Aberrant prothymocyte differentiation, T-cell receptor gene rearrangements, and nodal involvement. Arch Dermatol 126:1609–1616, 1990

    Google Scholar 

  44. Headington JT, Roth MS, Ginsburg D, Lichter AS, Hyder D, Schnitzer B: T-cell receptor gene rearrangement in regressing atypical histiocytosis. Arch Dermatol 123:1183–1187, 1987

    Google Scholar 

  45. Hytiroglou P, Phelps RG, Wattenberg DJ, Strauchen JA: Histiocytic cytophagic panniculitis: molecular evidence for a clonal T-cell disorder. J Am Acad Dermatol 27:333–336, 1992

    Google Scholar 

  46. Weiss LM, Wood GS, Trela M, Warnke RA, Sklar J: Clonal T-cell populations in lymphomatoid papulosis. Evidence of a lymphoproliferative origin for a clinically benign disease. N Engl J Med 315:475–479, 1986

    Google Scholar 

  47. Kadin ME, Vondeheid EC, Sako D, Clayton LK, Olbricht S: Clonal composition of T cells in lymphomatoid papulosis. Am J Pathol 126:13–17, 1987

    Google Scholar 

  48. Whittaker S, Smith N, Jones RR, Luzzatto L: Analysis of beta, gamma, and delta T-cell receptor genes in lymphomatoid papulosis: cellular basis of two distinct histologic subsets. J Invest Dermatol 96:786–</del>791, 1991

    Google Scholar 

  49. Zelickson BD, Peters MS, Muller SA, Thibodeau SN, Lust JA, Quam LM, Pittelkow MR: T-cell receptor gene rearrangement analysis: cutaneous T cell lymphoma, peripheral T cell lymphoma, and premalignant and benign cutaneous lymphoproliferative disorders. J Am Acad Dermatol 25:787–796, 1991

    Google Scholar 

  50. Mehregan DA, Gibson LE, Muller SA: Follicular mucinosis: Histopathologic review of 33 cases. Mayo Clin Proc 66:387–390, 1991

    Google Scholar 

  51. Weiss LM, Wood GS, Ellisen LW, Reynolds TC, Sklar J: Clonal T-cell populations in pityriasis lichenoideset varioliforms acuta (Mucha-Habe rmann disease ). Am J Pathol 126:417–421, 1987

    Google Scholar 

  52. Landa N, Zelickson BD, Peters MS, Muller SA, Pittelkow MR: Cutaneous lymphoma versus pseudolymphoma: gene rearrangement study of 21 cases with clinicopathologic correlation. J Invest Dermatol 96:569A, 1991

    Google Scholar 

  53. Rijlaarsdam U, Bakels V, van Oostveen LW, Gordijn RJ, Geerts ML, Meijer CJ, Willemze R: Demonstration of clonal immunoglobulin gene rearrangements in cutaneous B-cell lymphomas and pseudo-B-cell lymphomas: Differential diagnostic and pathogenetic aspects. J Invest Dermatol 99:749–754, 1992

    Google Scholar 

  54. Wood GS, Ngan BY, Tung R, Hoffman TE, Abel EA, Hoppe RT, Warnke RA, Cleary ML, Sklar J: Clonal rearrangements of immunoglobulin genes and progression to B cell lymphoma in cutaneous lymphoid hyperplasia. Am J Pathol 135:13–19, 1989

    Google Scholar 

  55. Doherty PJ, Yang SX, Laxer RM, Silverman ED, Inman R, Pan S: Evidence for clonal expansion of T cell receptor VgammaII1 T cells in the synovial fluid of patients with arthritis. J Immunol 149:295–299, 1992

    Google Scholar 

  56. Kossakowska AE, Eyton-Jones S, Urbanski SJ: Immunoglobulin and T-cell receptor gene rearrangements in lesions of mucosa-associated lymphoid tissue. Diagn Mol Pathol 2:233240, 1993

    Google Scholar 

  57. Lehman CM, Sarago C, Nasim S, Comerford J, Karcher DS, Garrett CT: Comparison of PCR with Southern hybridization for the routine detection of immunoglobulin heavy chain gene rearrangements. Am J Clin Pathol 103:171–176, 1995

    Google Scholar 

  58. Samoszuk M, Ramzi E, Ravel J: Disseminated persistent lymphoid hyperplasia containing Epste in-Barr virus and clonal rearrangements of DNA. Diagn Mol Pathol 2:57–60, 1993

    Google Scholar 

  59. Armes JE, Eades S, Southey MC, Ross BC, Carapetis JR, Chow CW, Venter DJ: Disseminated, multiclonal Epstein-Barr virus-associated lymphoproliferative disease in a patient with hematological and immunological anomalies. Diagn Mol Pathol 4:39–47, 1995

    Google Scholar 

  60. Calvert R, Randerson J, Evans P, Cawkwell R, Lewis F, Dixon MF, Jack A, Owen R, Shiach C, Morgan GJ: Genetic abnormalities during transition from Helicobacter-pylori-associated gastritis to low-grade MALToma. Lancet 345:26–27, 1995

    Google Scholar 

  61. Hsi ED, Greenson JK, Singleton TP, Siddiqui J, Schnitzer B, Ross CW: Detection of immunoglobulin heavy chain gene rearrangements by polymerase chain reaction in chronic active gastritis associted with Helicobacter pylori. Hum Pathol 27:290296, 1996

    Google Scholar 

  62. Weiss LM, Spagnolo DV: Assessment of clonality in lymphoid proliferations. Am J Pathol 142:1679–1682, 1993

    Google Scholar 

  63. Diaz-Cano S: PCR-based alternative for diagnosis of immunoglobulin heavy chain gene rearrangement. Principles, practice, and polemics. Diagn Mol Pathol 5:3–9, 1996

    Google Scholar 

  64. Inghirami G, Szablocs MJ, Yee HT, Corradini P, Cesarman E, Knowles DM: Detection of immunoglobulin gene re arrange-ment of B cell non-Hodgkin's lymphomas and leukemias in fresh, unfixed and formalin-fixed, paraffin-embedded tissue by polymerase chain reaction. Lab Invest 68:746757, 1993

    Google Scholar 

  65. Liang R, Chan V, Chan TK, Wong T, Chiu E, Lie A, Todd D: Detection of immunoglobulin gene rearrangements in lymphoid malignancies of B-cell lineage by seminested polymerase chain reaction gene amplification. Am J Hematol 43:24–28, 1993

    Google Scholar 

  66. Slack DN, McCarthy KP, Wiedemann LM, Sloane JP: Evaluation of sensitivity, specificity, and reproducibility of an optimized method for detecting clonal rearrangements of immunoglobulin and T-cell receptor genes in formalin-fixed, paraffin-embedded sections.Diagn Mol Pathol 2:223232, 1993

    Google Scholar 

  67. Yamada M, Hudson S, Tournay O, Bittenbender S, Shane SS, Lange B, Tsujimoto Y, Caton AJ, Rovera G: Detection of minimal disease in hematopoietic malignancies of the B-cell lineage by using third-complementarity-determining region (CDR-III)-specific probes. Proc Natl Acad Sci USA 86:5123–5127, 1989

    Google Scholar 

  68. Deane M, McCarthy KP, Wiedemann LM, Norton JD: An improved method for detection of B-lymphoid clonality by polymerase chain reaction. Leukemia 5:726–730, 1991

    Google Scholar 

  69. Medeiros LJ, Weiss LM: The utility of the polymerase chain reaction as a screening method for the detection of antigen receptor gene rearrangements. Hum Pathol 25:1261–1263, 1994

    Google Scholar 

Download references

Authors
  1. Allan P. Weston
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sushanta K. Banerjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rebecca T. Horvat
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rachel Cherian
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Donald R. Campbell
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mikhail N. Zoubine
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Weston, A.P., Banerjee, S.K., Horvat, R.T. et al. Specificity of Polymerase Chain Reaction Monoclonality for Diagnosis of Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma (Direct Comparison to Southern Blot Gene Rearrangement). Dig Dis Sci 43, 290–299 (1998). https://doi.org/10.1023/A:1018842002926

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1018842002926

Search

Navigation