Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1988 Dec;58(6):723–729. doi: 10.1038/bjc.1988.297

Phenotypic and genotypic heterogeneity of peripheral T-cell lymphoma.

J L Smith 1, D G Haegert 1, E Hodges 1, G N Stacey 1, W M Howell 1, D H Wright 1, D B Jones 1
PMCID: PMC2246885  PMID: 2852027

Abstract

A series of 21 phenotypically characterised T-cell lymphomas histologically defined as lymphocytic, lymphoblastic, immunoblastic, AILD type, pleomorphic, T-zone and Lennert's T-cell lymphoma, were investigated for T-cell receptor (TcR) and immunoglobulin (Ig) gene rearrangements. Phenotypic analyses of frozen sections and cell suspensions were heterogeneous and in many cases no single T-cell marker recognised all of the malignant cells. Data derived by staining with antibodies reactive with antigens in paraffin embedded tissue were consistent with T NHL in all cases except lymphoblastic lymphoma. TcR gene rearrangements were observed in lymphocytic, lymphoblastic and immunoblastic lymphoma, however, in the remaining 14 phenotypically and histologically defined peripheral T-cell lymphomas, 2 showed rearrangement of TcR gamma and beta genes consistent with T NHL and 2 showed Ig JH rearrangements only, suggestive of either reactive T-cell populations masking cryptic disease or presence of tumour populations with aberrant gene rearrangement and expression of T lineage antigens. No Ig or TcR gene rearrangements were found in the remaining 10 cases, in which morphologically identifiable tumour cells comprised 10-90% of the cell population. In 3/6 cases tested some CD3 positive cells failed to stain with WT31 or beta F1, monoclonal antibodies that recognise determinants on combined TcR gamma beta or TcR beta chains respectively. Whether these cases represent tumours arising from an undetermined cell of origin or polyclonal expansions of T-cells remains to be determined. Our results confirm the phenotypic heterogeneity of histologically defined peripheral T-cell lymphoma and indicate that in these particular histological subtypes gene rearrangement analysis can also yield heterogeneous results which may be unhelpful in determining cell lineage and clonality.

Full text

PDF
729

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnold A., Cossman J., Bakhshi A., Jaffe E. S., Waldmann T. A., Korsmeyer S. J. Immunoglobulin-gene rearrangements as unique clonal markers in human lymphoid neoplasms. N Engl J Med. 1983 Dec 29;309(26):1593–1599. doi: 10.1056/NEJM198312293092601. [DOI] [PubMed] [Google Scholar]
  2. Borowitz M. J., Reichert T. A., Brynes R. K., Cousar J. B., Whitcomb C. C., Collins R. D., Crissman J. D., Byrne G. E., Jr The phenotypic diversity of peripheral T-cell lymphomas: the Southeastern Cancer Study Group experience. Hum Pathol. 1986 Jun;17(6):567–574. doi: 10.1016/s0046-8177(86)80128-9. [DOI] [PubMed] [Google Scholar]
  3. Brenner M. B., McLean J., Scheft H., Warnke R. A., Jones N., Strominger J. L. Characterization and expression of the human alpha beta T cell receptor by using a framework monoclonal antibody. J Immunol. 1987 Mar 1;138(5):1502–1509. [PubMed] [Google Scholar]
  4. Campana D., Thompson J. S., Amlot P., Brown S., Janossy G. The cytoplasmic expression of CD3 antigens in normal and malignant cells of the T lymphoid lineage. J Immunol. 1987 Jan 15;138(2):648–655. [PubMed] [Google Scholar]
  5. Cleary M. L., Chao J., Warnke R., Sklar J. Immunoglobulin gene rearrangement as a diagnostic criterion of B-cell lymphoma. Proc Natl Acad Sci U S A. 1984 Jan;81(2):593–597. doi: 10.1073/pnas.81.2.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Doggett R. S., Wood G. S., Horning S., Levy R., Dorfman R. F., Bindl J., Warnke R. A. The immunologic characterization of 95 nodal and extranodal diffuse large cell lymphomas in 89 patients. Am J Pathol. 1984 May;115(2):245–252. [PMC free article] [PubMed] [Google Scholar]
  7. Ekramoddoullah A. K., Kisil F. T., Sehon A. H. Partial characterization of an antigenic site of high molecular weight basic antigen, a ryegrass pollen allergen, using a monoclonal antibody. Mol Immunol. 1986 Feb;23(2):111–117. doi: 10.1016/0161-5890(86)90031-3. [DOI] [PubMed] [Google Scholar]
  8. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  9. Flanagan J. G., Rabbitts T. H. The sequence of a human immunoglobulin epsilon heavy chain constant region gene, and evidence for three non-allelic genes. EMBO J. 1982;1(5):655–660. doi: 10.1002/j.1460-2075.1982.tb01223.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Foa R., Casorati G., Giubellino M. C., Basso G., Schirò R., Pizzolo G., Lauria F., Lefranc M. P., Rabbitts T. H., Migone N. Rearrangements of immunoglobulin and T cell receptor beta and gamma genes are associated with terminal deoxynucleotidyl transferase expression in acute myeloid leukemia. J Exp Med. 1987 Mar 1;165(3):879–890. doi: 10.1084/jem.165.3.879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Foroni L., Catovsky D., Rabbitts T. H., Luzzatto L. DNA rearrangements of immunoglobulin genes correlate with phenotypic markers in B-cell malignancies. Mol Biol Med. 1984 Feb;2(1):63–79. [PubMed] [Google Scholar]
  12. Greaves M. F. Analysis of the clinical and biological significance of lymphoid phenotypes in acute leukemia. Cancer Res. 1981 Nov;41(11 Pt 2):4752–4766. [PubMed] [Google Scholar]
  13. Grogan T. M., Fielder K., Rangel C., Jolley C. J., Wirt D. P., Hicks M. J., Miller T. P., Brooks R., Greenberg B., Jones S. Peripheral T-cell lymphoma: aggressive disease with heterogeneous immunotypes. Am J Clin Pathol. 1985 Mar;83(3):279–288. doi: 10.1093/ajcp/83.3.279. [DOI] [PubMed] [Google Scholar]
  14. Haegert D. G., Furlong M. D., Smith J. L. Co-expression of surface immunoglobulin and T3 on hairy cells. Scand J Haematol. 1986 Sep;37(3):196–202. doi: 10.1111/j.1600-0609.1986.tb02297.x. [DOI] [PubMed] [Google Scholar]
  15. Haegert D. G., Smith J. L. Co-expression of T3 and surface immunoglobulin in neoplasms of 'early' B cells: a report of 2 cases. Eur J Haematol. 1987 Mar;38(3):213–219. doi: 10.1111/j.1600-0609.1987.tb01166.x. [DOI] [PubMed] [Google Scholar]
  16. Huck S., Lefranc M. P. Rearrangements to the JP1, JP and JP2 segments in the human T-cell rearranging gamma gene (TRG gamma) locus. FEBS Lett. 1987 Nov 30;224(2):291–296. doi: 10.1016/0014-5793(87)80472-6. [DOI] [PubMed] [Google Scholar]
  17. Jones D. B., Wright D. H., Paul F., Smith J. L. Phenotypic heterogeneity displayed by T-non Hodgkin's lymphoma (T-NHL) cells dispersed from diagnostic lymph node biopsies. Hematol Oncol. 1986 Jul-Sep;4(3):219–226. doi: 10.1002/hon.2900040306. [DOI] [PubMed] [Google Scholar]
  18. Knowles D. M., 2nd, Halper J. P. Human T-cell malignancies: Correlative clinical, histopathologic, immunologic, and cytochemical analysis of 23 cases. Am J Pathol. 1982 Feb;106(2):187–203. [PMC free article] [PubMed] [Google Scholar]
  19. Knowles D. M., 2nd The human T-cell leukemias: clinical, cytomorphologic, immunophenotypic, and genotypic characteristics. Hum Pathol. 1986 Jan;17(1):14–33. doi: 10.1016/s0046-8177(86)80151-4. [DOI] [PubMed] [Google Scholar]
  20. Korsmeyer S. J. Antigen receptor genes as molecular markers of lymphoid neoplasms. J Clin Invest. 1987 May;79(5):1291–1295. doi: 10.1172/JCI112951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lefranc M. P., Rabbitts T. H. Two tandemly organized human genes encoding the T-cell gamma constant-region sequences show multiple rearrangement in different T-cell types. Nature. 1985 Aug 1;316(6027):464–466. doi: 10.1038/316464a0. [DOI] [PubMed] [Google Scholar]
  22. Minden M. D., Mak T. W. The structure of the T cell antigen receptor genes in normal and malignant T cells. Blood. 1986 Aug;68(2):327–336. [PubMed] [Google Scholar]
  23. O'Connor N. T., Wainscoat J. S., Weatherall D. J., Gatter K. C., Feller A. C., Isaacson P., Jones D., Lennert K., Pallesen G., Ramsey A. Rearrangement of the T-cell-receptor beta-chain gene in the diagnosis of lymphoproliferative disorders. Lancet. 1985 Jun 8;1(8441):1295–1297. doi: 10.1016/s0140-6736(85)92791-6. [DOI] [PubMed] [Google Scholar]
  24. Pelicci P. G., Knowles D. M., 2nd, Dalla Favera R. Lymphoid tumors displaying rearrangements of both immunoglobulin and T cell receptor genes. J Exp Med. 1985 Sep 1;162(3):1015–1024. doi: 10.1084/jem.162.3.1015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Picker L. J., Brenner M. B., Weiss L. M., Smith S. D., Warnke R. A. Discordant expression of CD3 and T-cell receptor beta-chain antigens in T-lineage lymphomas. Am J Pathol. 1987 Dec;129(3):434–440. [PMC free article] [PubMed] [Google Scholar]
  26. Poppema S., Hollema H., Visser L., Vos H. Monoclonal antibodies (MT1, MT2, MB1, MB2, MB3) reactive with leukocyte subsets in paraffin-embedded tissue sections. Am J Pathol. 1987 Jun;127(3):418–429. [PMC free article] [PubMed] [Google Scholar]
  27. Rabbitts T. H., Forster A., Matthews J. G. The breakpoint of the Philadelphia chromosome 22 in chronic myeloid leukaemia is distal to the immunoglobulin lambda light chain constant region genes. Mol Biol Med. 1983 Jul;1(1):11–19. [PubMed] [Google Scholar]
  28. Ramsay A. D., Smith W. J., Earl H. M., Souhami R. L., Isaacson P. G. T-cell lymphomas in adults: a clinicopathological study of eighteen cases. J Pathol. 1987 Jun;152(2):63–76. doi: 10.1002/path.1711520202. [DOI] [PubMed] [Google Scholar]
  29. Royer H. D., Reinherz E. L. T lymphocytes: ontogeny, function, and relevance to clinical disorders. N Engl J Med. 1987 Oct 29;317(18):1136–1142. doi: 10.1056/NEJM198710293171807. [DOI] [PubMed] [Google Scholar]
  30. Smith S. H., Brown M. H., Rowe D., Callard R. E., Beverley P. C. Functional subsets of human helper-inducer cells defined by a new monoclonal antibody, UCHL1. Immunology. 1986 May;58(1):63–70. [PMC free article] [PubMed] [Google Scholar]
  31. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  32. Spits H., Borst J., Tax W., Capel P. J., Terhorst C., de Vries J. E. Characteristics of a monoclonal antibody (WT-31) that recognizes a common epitope on the human T cell receptor for antigen. J Immunol. 1985 Sep;135(3):1922–1928. [PubMed] [Google Scholar]
  33. Stein H., Lennert K., Feller A. C., Mason D. Y. Immunohistological analysis of human lymphoma: correlation of histological and immunological categories. Adv Cancer Res. 1984;42:67–147. doi: 10.1016/s0065-230x(08)60456-x. [DOI] [PubMed] [Google Scholar]
  34. Stevenson F. K., George A. J., Walters M. T., Hamblin T. J. Analysis of soluble HLA class II antigenic material in patients with immunological diseases using monoclonal antibodies. J Immunol Methods. 1986 Feb 12;86(2):187–190. doi: 10.1016/0022-1759(86)90451-5. [DOI] [PubMed] [Google Scholar]
  35. Suchi T., Lennert K., Tu L. Y., Kikuchi M., Sato E., Stansfeld A. G., Feller A. C. Histopathology and immunohistochemistry of peripheral T cell lymphomas: a proposal for their classification. J Clin Pathol. 1987 Sep;40(9):995–1015. doi: 10.1136/jcp.40.9.995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Warnke R. A., Rouse R. V. Limitations encountered in the application of tissue section immunodiagnosis to the study of lymphomas and related disorders. Hum Pathol. 1985 Apr;16(4):326–331. doi: 10.1016/s0046-8177(85)80226-4. [DOI] [PubMed] [Google Scholar]
  37. Weiss L. M., Picker L. J., Grogan T. M., Warnke R. A., Sklar J. Absence of clonal beta and gamma T-cell receptor gene rearrangements in a subset of peripheral T-cell lymphomas. Am J Pathol. 1988 Mar;130(3):436–442. [PMC free article] [PubMed] [Google Scholar]
  38. Winberg C. D., Sheibani K., Krance R., Rappaport H. Peripheral T cell lymphoma: immunologic and cell-kinetic observations associated with morphological progression. Blood. 1985 Oct;66(4):980–989. [PubMed] [Google Scholar]
  39. Wright D. H. T-cell lymphomas. Histopathology. 1986 Mar;10(3):321–326. doi: 10.1111/j.1365-2559.1986.tb02486.x. [DOI] [PubMed] [Google Scholar]
  40. Yanagi Y., Yoshikai Y., Leggett K., Clark S. P., Aleksander I., Mak T. W. A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains. Nature. 1984 Mar 8;308(5955):145–149. doi: 10.1038/308145a0. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES