Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1998 Mar;152(3):683–689.

Detection of HTLV-1 by polymerase chain reaction in situ hybridization in adult T-cell leukemia/lymphoma.

M Setoyama 1, F A Kerdel 1, G Elgart 1, T Kanzaki 1, J J Byrnes 1
PMCID: PMC1858394  PMID: 9502410

Abstract

A method for nonradioactive polymerase chain reaction in situ hybridization was developed and used to determine the distribution of human T-lymphotropic virus type I (HTLV-I) proviral DNA in paraffin-embedded surgical specimens of adult T-cell leukemia/lymphoma (ATLL). As controls, we used biopsy samples of five cases of mycosis fungoides, cells of an HTLV-I-infected cell line (MT2), as well as HTLV-1-negative cells (YAS). We successfully detected the amplicon of the HTLV-1 tax sequence in the nuclei of the cutaneous infiltrating lymphoid cells in 90% (9/10) of ATLL cases. Studies also revealed the existence of HTLV-1 provirus DNA in nuclei of sweat gland epithelial cells and vascular endothelial cells as well as lymphoid cells in ATLL patients. Mycosis fungoides and YAS cells were negative for the HTLV-I tax sequence, but MT2 cells were strongly positive. The results indicated that this technique was more sensitive in detecting intracellular amplicons than was the previous in situ hybridization method. Through its use, we were able to easily determine the distribution of HTLV-I-positive cells among the various cells and tissues of paraffin-embedded archival materials.

Full text

PDF
683

Images in this article

685Figure 1
on p.685
686Figure 2
on p.686
686Figure 3
on p.686
687Figure 4
on p.687
687Figure 5
on p.687

Selected References

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

  1. Bagasra O., Hauptman S. P., Lischner H. W., Sachs M., Pomerantz R. J. Detection of human immunodeficiency virus type 1 provirus in mononuclear cells by in situ polymerase chain reaction. N Engl J Med. 1992 May 21;326(21):1385–1391. doi: 10.1056/NEJM199205213262103. [DOI] [PubMed] [Google Scholar]
  2. Bagasra O., Seshamma T., Pomerantz R. J. Polymerase chain reaction in situ: intracellular amplification and detection of HIV-1 proviral DNA and other specific genes. J Immunol Methods. 1993 Jan 14;158(1):131–145. doi: 10.1016/0022-1759(93)90265-9. [DOI] [PubMed] [Google Scholar]
  3. Boshoff C., Schulz T. F., Kennedy M. M., Graham A. K., Fisher C., Thomas A., McGee J. O., Weiss R. A., O'Leary J. J. Kaposi's sarcoma-associated herpesvirus infects endothelial and spindle cells. Nat Med. 1995 Dec;1(12):1274–1278. doi: 10.1038/nm1295-1274. [DOI] [PubMed] [Google Scholar]
  4. Chen Y. X., Ikeda S., Mori H., Hata T., Tsukasaki K., Momita S., Yamada Y., Kamihira S., Mine M., Tomonaga M. Molecular detection of pre-ATL state among healthy HTLV-1 carriers in an endemic area of Japan. Int J Cancer. 1995 Mar 16;60(6):798–801. doi: 10.1002/ijc.2910600612. [DOI] [PubMed] [Google Scholar]
  5. Ciampolillo A., Marini V., Mirakian R., Buscema M., Schulz T., Pujol-Borrell R., Bottazzo G. F. Retrovirus-like sequences in Graves' disease: implications for human autoimmunity. Lancet. 1989 May 20;1(8647):1096–1100. doi: 10.1016/s0140-6736(89)92382-9. [DOI] [PubMed] [Google Scholar]
  6. Embretson J., Zupancic M., Beneke J., Till M., Wolinsky S., Ribas J. L., Burke A., Haase A. T. Analysis of human immunodeficiency virus-infected tissues by amplification and in situ hybridization reveals latent and permissive infections at single-cell resolution. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):357–361. doi: 10.1073/pnas.90.1.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hamada T., Setoyama M., Katahira Y., Furuno T., Fujiyoshi T., Sonoda S., Tashiro M. Differences in HTLV-I integration patterns between skin lesions and peripheral blood lymphocytes of HTLV-I seropositive patients with cutaneous lymphoproliferative disorders. J Dermatol Sci. 1992 Sep;4(2):76–82. doi: 10.1016/0923-1811(92)90062-g. [DOI] [PubMed] [Google Scholar]
  8. Höllsberg P., Hafler D. A. What is the pathogenesis of human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis? Ann Neurol. 1995 Feb;37(2):143–145. doi: 10.1002/ana.410370203. [DOI] [PubMed] [Google Scholar]
  9. Katahira Y., Yashiki S., Fujiyoshi T., Nomura K., Tara M., Mori M., Setoyama M., Kanzaki T., Shida H., Sonoda S. In vitro induction of cytotoxic T lymphocytes against HTLV-I-infected T-cells from adult T-cell leukemia patients, asymptomatic HTLV-I carriers and seronegative healthy donors. Jpn J Cancer Res. 1995 Jan;86(1):21–27. doi: 10.1111/j.1349-7006.1995.tb02983.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Khan Z. M., Sebenik M., Zucker-Franklin D. Localization of human T-cell lymphotropic virus-1 tax proviral sequences in skin biopsies of patients with mycosis fungoides by in situ polymerase chain reaction. J Invest Dermatol. 1996 Apr;106(4):667–672. doi: 10.1111/1523-1747.ep12345488. [DOI] [PubMed] [Google Scholar]
  11. Kikuchi A., Nishikawa T., Yamaguchi K. Absence of human T-cell lymphotropic virus type I in cutaneous T-cell lymphoma. N Engl J Med. 1997 Jan 23;336(4):296–297. doi: 10.1056/NEJM199701233360415. [DOI] [PubMed] [Google Scholar]
  12. LaGrenade L., Hanchard B., Fletcher V., Cranston B., Blattner W. Infective dermatitis of Jamaican children: a marker for HTLV-I infection. Lancet. 1990 Dec 1;336(8727):1345–1347. doi: 10.1016/0140-6736(90)92896-p. [DOI] [PubMed] [Google Scholar]
  13. Levin M. C., Fox R. J., Lehky T., Walter M., Fox C. H., Flerlage N., Bamford R., Jacobson S. PCR-in situ hybridization detection of human T-cell lymphotropic virus type 1 (HTLV-1) tax proviral DNA in peripheral blood lymphocytes of patients with HTLV-1-associated neurologic disease. J Virol. 1996 Feb;70(2):924–933. doi: 10.1128/jvi.70.2.924-933.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Long A. A., Komminoth P., Lee E., Wolfe H. J. Comparison of indirect and direct in-situ polymerase chain reaction in cell preparations and tissue sections. Detection of viral DNA, gene rearrangements and chromosomal translocations. Histochemistry. 1993 Feb;99(2):151–162. doi: 10.1007/BF00571876. [DOI] [PubMed] [Google Scholar]
  15. Mochizuki M., Watanabe T., Yamaguchi K., Takatsuki K., Yoshimura K., Shirao M., Nakashima S., Mori S., Araki S., Miyata N. HTLV-I uveitis: a distinct clinical entity caused by HTLV-I. Jpn J Cancer Res. 1992 Mar;83(3):236–239. doi: 10.1111/j.1349-7006.1992.tb00092.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mochizuki M., Watanabe T., Yamaguchi K., Yoshimura K., Nakashima S., Shirao M., Araki S., Takatsuki K., Mori S., Miyata N. Uveitis associated with human T-cell lymphotropic virus type I. Am J Ophthalmol. 1992 Aug 15;114(2):123–129. doi: 10.1016/s0002-9394(14)73974-1. [DOI] [PubMed] [Google Scholar]
  17. Nakada K., Yamaguchi K., Furugen S., Nakasone T., Nakasone K., Oshiro Y., Kohakura M., Hinuma Y., Seiki M., Yoshida M. Monoclonal integration of HTLV-I proviral DNA in patients with strongyloidiasis. Int J Cancer. 1987 Aug 15;40(2):145–148. doi: 10.1002/ijc.2910400203. [DOI] [PubMed] [Google Scholar]
  18. Nishioka K., Maruyama I., Sato K., Kitajima I., Nakajima Y., Osame M. Chronic inflammatory arthropathy associated with HTLV-I. Lancet. 1989 Feb 25;1(8635):441–441. doi: 10.1016/s0140-6736(89)90038-x. [DOI] [PubMed] [Google Scholar]
  19. Nuovo G. J., Gallery F., Hom R., MacConnell P., Bloch W. Importance of different variables for enhancing in situ detection of PCR-amplified DNA. PCR Methods Appl. 1993 May;2(4):305–312. doi: 10.1101/gr.2.4.305. [DOI] [PubMed] [Google Scholar]
  20. Nuovo G. J., Gallery F., MacConnell P., Becker J., Bloch W. An improved technique for the in situ detection of DNA after polymerase chain reaction amplification. Am J Pathol. 1991 Dec;139(6):1239–1244. [PMC free article] [PubMed] [Google Scholar]
  21. Ohshima K., Kikuchi M., Masuda Y., Sumiyoshi Y., Eguchi F., Mohtai H., Takeshita M., Kimura N. Human T-cell leukemia virus type I associated lymphadenitis. Cancer. 1992 Jan 1;69(1):239–248. doi: 10.1002/1097-0142(19920101)69:1<239::aid-cncr2820690139>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
  22. Osame M., Usuku K., Izumo S., Ijichi N., Amitani H., Igata A., Matsumoto M., Tara M. HTLV-I associated myelopathy, a new clinical entity. Lancet. 1986 May 3;1(8488):1031–1032. doi: 10.1016/s0140-6736(86)91298-5. [DOI] [PubMed] [Google Scholar]
  23. Patel V. G., Shum-Siu A., Heniford B. W., Wieman T. J., Hendler F. J. Detection of epidermal growth factor receptor mRNA in tissue sections from biopsy specimens using in situ polymerase chain reaction. Am J Pathol. 1994 Jan;144(1):7–14. [PMC free article] [PubMed] [Google Scholar]
  24. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  25. Setoyama M., Fujiyoshi T., Mizoguchi S., Katahira Y., Yashiki S., Tara M., Kanzaki T., Sonoda S. HTLV-I messenger RNA is expressed in vivo in adult T-cell leukemia/lymphoma patients: an in situ hybridization study. Int J Cancer. 1994 Jun 1;57(5):760–764. doi: 10.1002/ijc.2910570525. [DOI] [PubMed] [Google Scholar]
  26. Shimoyama M. Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87). Br J Haematol. 1991 Nov;79(3):428–437. doi: 10.1111/j.1365-2141.1991.tb08051.x. [DOI] [PubMed] [Google Scholar]
  27. Sonoda S., Fujiyoshi T., Yashiki S. Immunogenetics of HTLV-I/II and associated diseases. J Acquir Immune Defic Syndr Hum Retrovirol. 1996;13 (Suppl 1):S119–S123. doi: 10.1097/00042560-199600001-00020. [DOI] [PubMed] [Google Scholar]
  28. Sugimoto M., Nakashima H., Watanabe S., Uyama E., Tanaka F., Ando M., Araki S., Kawasaki S. T-lymphocyte alveolitis in HTLV-I-associated myelopathy. Lancet. 1987 Nov 21;2(8569):1220–1220. doi: 10.1016/s0140-6736(87)91362-6. [DOI] [PubMed] [Google Scholar]
  29. Tajima K. The 4th nation-wide study of adult T-cell leukemia/lymphoma (ATL) in Japan: estimates of risk of ATL and its geographical and clinical features. The T- and B-cell Malignancy Study Group. Int J Cancer. 1990 Feb 15;45(2):237–243. doi: 10.1002/ijc.2910450206. [DOI] [PubMed] [Google Scholar]
  30. Terada K., Katamine S., Eguchi K., Moriuchi R., Kita M., Shimada H., Yamashita I., Iwata K., Tsuji Y., Nagataki S. Prevalence of serum and salivary antibodies to HTLV-1 in Sjögren's syndrome. Lancet. 1994 Oct 22;344(8930):1116–1119. doi: 10.1016/s0140-6736(94)90630-0. [DOI] [PubMed] [Google Scholar]
  31. van der Valk P. G., Hollema H., van Voorst Vander P. C., Brinker M. G., Poppema S. Sjögren's syndrome with specific cutaneous manifestations and multifocal clonal T-cell populations progressing to a cutaneous pleomorphic T-cell lymphoma. Am J Clin Pathol. 1989 Sep;92(3):357–361. doi: 10.1093/ajcp/92.3.357. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES