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. 1999 Nov-Dec;72(6):365–375.

Evaluation of T-cell receptor gene rearrangements in patients with recurrent patch/plaque (T2) CTCL (mycosis fungoides).

M Thayu 1, G Tallini 1, E J Glusac 1, B M Kacinski 1, L D Wilson 1
PMCID: PMC2579043  PMID: 11138932

Abstract

Cutaneous T-cell lymphoma is typically a clonal neoplasm of epidermotropic CD4+ T-lymphocytes that includes the entity mycosis fungoides (MF). After identification of patients with recurrent MF treated with total skin electron beam therapy (TSEBT) at the Yale University School of Medicine, this study attempted to compare T-cell receptor (TCR) gamma gene rearrangements via polymerase chain reaction (PCR) in both original and recurrent skin biopsies from these patients. Between 1974 and 1996, a total of 95 T2 MF patients were treated with TSEB, and four of these were identified for the study. Slides and tissue samples of both primary and recurrent skin biopsies for each patient were confirmed as being consistent with ME DNA for PCR was isolated from paraffin-embedded tissue samples. Using consensus primers that hybridize with conserved regions of the TCR gene, these regions of the genome were amplified. The PCR products were then analyzed by acrylamide gel electrophoresis. Of the primary and recurrent samples from four patients with a median disease-free interval (DFI) of 1222 days, only two showed evidence of a dominant TCR clone. A number of factors, including lack of sequence homology between the primers and the gene segments, the existence of multiple neoplastic cell lines, DNA degradation in the archival samples, and the presence of reactive as well as malignant lymphocytes, may have prevented the detection of dominant TCR rearranged clones in the samples. Despite the results of this study, TCR analysis via PCR and gel electrophoresis continues to be of utility in the evaluation of patients with MF when used in conjunction with other diagnostic modalities and in cases with nonspecific clinical, histopathological, and immunophenotyping findings.

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Selected References

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  1. Abel E. A., Sendagorta E., Hoppe R. T., Hu C. H. PUVA treatment of erythrodermic and plaque-type mycosis fungoides. Ten-year follow-up study. Arch Dermatol. 1987 Jul;123(7):897–901. [PubMed] [Google Scholar]
  2. Benhattar J., Delacretaz F., Martin P., Chaubert P., Costa J. Improved polymerase chain reaction detection of clonal T-cell lymphoid neoplasms. Diagn Mol Pathol. 1995 Jun;4(2):108–112. doi: 10.1097/00019606-199506000-00006. [DOI] [PubMed] [Google Scholar]
  3. Braverman I. M., Yager N. B., Chen M., Cadman E. C., Hait W. N., Maynard T. Combined total body electron beam irradiation and chemotherapy for mycosis fungoides. J Am Acad Dermatol. 1987 Jan;16(1 Pt 1):45–60. doi: 10.1016/s0190-9622(87)70004-8. [DOI] [PubMed] [Google Scholar]
  4. Bunn P. A., Jr, Hoffman S. J., Norris D., Golitz L. E., Aeling J. L. Systemic therapy of cutaneous T-cell lymphomas (mycosis fungoides and the Sézary syndrome). Ann Intern Med. 1994 Oct 15;121(8):592–602. doi: 10.7326/0003-4819-121-8-199410150-00007. [DOI] [PubMed] [Google Scholar]
  5. Bunn P. A., Jr, Lamberg S. I. Report of the Committee on Staging and Classification of Cutaneous T-Cell Lymphomas. Cancer Treat Rep. 1979 Apr;63(4):725–728. [PubMed] [Google Scholar]
  6. Dalton J. A., Yag-Howard C., Messina J. L., Glass L. F. Cutaneous T-cell lymphoma. Int J Dermatol. 1997 Nov;36(11):801–809. doi: 10.1046/j.1365-4362.1997.00329.x. [DOI] [PubMed] [Google Scholar]
  7. Edelson R., Berger C., Gasparro F., Jegasothy B., Heald P., Wintroub B., Vonderheid E., Knobler R., Wolff K., Plewig G. Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N Engl J Med. 1987 Feb 5;316(6):297–303. doi: 10.1056/NEJM198702053160603. [DOI] [PubMed] [Google Scholar]
  8. Heald P. W., Edelson R. L. Photopheresis for T cell mediated diseases. Adv Dermatol. 1988;3:25–40. [PubMed] [Google Scholar]
  9. Herrmann J. J., Roenigk H. H., Jr, Hönigsmann H. Ultraviolet radiation for treatment of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am. 1995 Oct;9(5):1077–1088. [PubMed] [Google Scholar]
  10. Hoppe R. T., Fuks Z., Bagshaw M. A. Radiation therapy in the management of cutaneous T-cell lymphomas. Cancer Treat Rep. 1979 Apr;63(4):625–632. [PubMed] [Google Scholar]
  11. Hönigsmann H., Brenner W., Rauschmeier W., Konrad K., Wolff K. Photochemotherapy for cutaneous T cell lymphoma. A follow-up study. J Am Acad Dermatol. 1984 Feb;10(2 Pt 1):238–245. doi: 10.1016/s0190-9622(84)70030-2. [DOI] [PubMed] [Google Scholar]
  12. Jones G. W., Hoppe R. T., Glatstein E. Electron beam treatment for cutaneous T-cell lymphoma. Hematol Oncol Clin North Am. 1995 Oct;9(5):1057–1076. [PubMed] [Google Scholar]
  13. Jones G. W., Rosenthal D., Wilson L. D. Total skin electron radiation for patients with erythrodermic cutaneous T-cell lymphoma (mycosis fungoides and the Sézary syndrome). Cancer. 1999 May 1;85(9):1985–1995. doi: 10.1002/(sici)1097-0142(19990501)85:9<1985::aid-cncr16>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
  14. Koch S. E., Zackheim H. S., Williams M. L., Fletcher V., LeBoit P. E. Mycosis fungoides beginning in childhood and adolescence. J Am Acad Dermatol. 1987 Oct;17(4):563–570. doi: 10.1016/s0190-9622(87)70238-2. [DOI] [PubMed] [Google Scholar]
  15. Koh H. K., Charif M., Weinstock M. A. Epidemiology and clinical manifestations of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am. 1995 Oct;9(5):943–960. [PubMed] [Google Scholar]
  16. Lee P. Y., Charley M., Tharp M., Jegasothy B. V., Deng J. S. Possible role of Epstein-Barr virus infection in cutaneous T-cell lymphomas. J Invest Dermatol. 1990 Sep;95(3):309–312. doi: 10.1111/1523-1747.ep12485017. [DOI] [PubMed] [Google Scholar]
  17. Neri A., Fracchiolla N. S., Roscetti E., Garatti S., Trecca D., Boletini A., Perletti L., Baldini L., Maiolo A. T., Berti E. Molecular analysis of cutaneous B- and T-cell lymphomas. Blood. 1995 Oct 15;86(8):3160–3172. [PubMed] [Google Scholar]
  18. Peters M. S., Thibodeau S. N., White J. W., Jr, Winkelmann R. K. Mycosis fungoides in children and adolescents. J Am Acad Dermatol. 1990 Jun;22(6 Pt 1):1011–1018. doi: 10.1016/0190-9622(90)70143-6. [DOI] [PubMed] [Google Scholar]
  19. Quirós P. A., Jones G. W., Kacinski B. M., Braverman I. M., Heald P. W., Edelson R. L., Wilson L. D. Total skin electron beam therapy followed by adjuvant psoralen/ultraviolet-A light in the management of patients with T1 and T2 cutaneous T-cell lymphoma (mycosis fungoides). Int J Radiat Oncol Biol Phys. 1997 Jul 15;38(5):1027–1035. doi: 10.1016/s0360-3016(97)00127-2. [DOI] [PubMed] [Google Scholar]
  20. Ramsay D. L., Meller J. A., Zackheim H. S. Topical treatment of early cutaneous T-cell lymphoma. Hematol Oncol Clin North Am. 1995 Oct;9(5):1031–1056. [PubMed] [Google Scholar]
  21. Scheller U., Muche J. M., Sterry W., Lukowsky A. Detection of clonal T cells in cutaneous T cell lymphoma by polymerase chain reaction: comparison of mutation detection enhancement-polyacrylamide gel electrophoresis, temperature gradient gel electrophoresis and fragment analysis of sequencing gels. Electrophoresis. 1998 May;19(5):653–658. doi: 10.1002/elps.1150190507. [DOI] [PubMed] [Google Scholar]
  22. Sinha A. A., Heald P. Advances in the management of cutaneous T-cell lymphoma. Dermatol Clin. 1998 Apr;16(2):301–311. doi: 10.1016/s0733-8635(05)70012-7. [DOI] [PubMed] [Google Scholar]
  23. Slack D. N., McCarthy K. P., Wiedemann L. M., Sloane J. P. 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. 1993 Dec;2(4):223–232. [PubMed] [Google Scholar]
  24. Spittle M. F. Mycosis fungoides: electron beam therapy in England. Cancer Treat Rep. 1979 Apr;63(4):639–641. [PubMed] [Google Scholar]
  25. Thor Straten P., Ralfkiaer E., Hendriks J., Seremet T., Vejlsgaard G. L., Zeuthen J. T-cell receptor variable region genes in cutaneous T-cell lymphomas. Br J Dermatol. 1998 Jan;138(1):3–12. doi: 10.1046/j.1365-2133.1998.02022.x. [DOI] [PubMed] [Google Scholar]
  26. Tuyp E., Burgoyne A., Aitchison T., MacKie R. A case-control study of possible causative factors in mycosis fungoides. Arch Dermatol. 1987 Feb;123(2):196–200. [PubMed] [Google Scholar]
  27. Weinstock M. A., Horm J. W. Mycosis fungoides in the United States. Increasing incidence and descriptive epidemiology. JAMA. 1988 Jul 1;260(1):42–46. [PubMed] [Google Scholar]
  28. Weinstock M. A., Reynes J. F. The changing survival of patients with mycosis fungoides: a population-based assessment of trends in the United States. Cancer. 1999 Jan 1;85(1):208–212. [PubMed] [Google Scholar]
  29. Whittaker S. T-cell receptor gene analysis in cutaneous T-cell lymphomas. Clin Exp Dermatol. 1996 Mar;21(2):81–87. [PubMed] [Google Scholar]
  30. Whittemore A. S., Holly E. A., Lee I. M., Abel E. A., Adams R. M., Nickoloff B. J., Bley L., Peters J. M., Gibney C. Mycosis fungoides in relation to environmental exposures and immune response: a case-control study. J Natl Cancer Inst. 1989 Oct 18;81(20):1560–1567. doi: 10.1093/jnci/81.20.1560. [DOI] [PubMed] [Google Scholar]
  31. Wilson L. D., Quiros P. A., Kolenik S. A., Heald P. W., Braverman I. M., Edelson R. L., Kacinski B. M. Additional courses of total skin electron beam therapy in the treatment of patients with recurrent cutaneous T-cell lymphoma. J Am Acad Dermatol. 1996 Jul;35(1):69–73. doi: 10.1016/S0190-9622(96)90499-5. [DOI] [PubMed] [Google Scholar]
  32. Wood G. S., Tung R. M., Haeffner A. C., Crooks C. F., Liao S., Orozco R., Veelken H., Kadin M. E., Koh H., Heald P. Detection of clonal T-cell receptor gamma gene rearrangements in early mycosis fungoides/Sezary syndrome by polymerase chain reaction and denaturing gradient gel electrophoresis (PCR/DGGE). J Invest Dermatol. 1994 Jul;103(1):34–41. doi: 10.1111/1523-1747.ep12389114. [DOI] [PubMed] [Google Scholar]
  33. Zelickson B. D., Peters M. S., Muller S. A., Thibodeau S. N., Lust J. A., Quam L. M., Pittelkow M. R. 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. 1991 Nov;25(5 Pt 1):787–796. doi: 10.1016/s0190-9622(08)80970-x. [DOI] [PubMed] [Google Scholar]

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