Abstract
AIMS: To examine the immunohistochemical distribution of thymidine phosphorylase (TP) in all clinicopathological subtypes of Kaposi sarcoma. METHODS: Thirty two biopsy specimens of Kaposi sarcoma (29 patients) were studied. Six of these patients represented classic, six endemic, eight HIV associated, seven post-immunosuppression/transplant related, and two unclassified variants of Kaposi sarcoma. The average age was 49 years (range 22-83 years) and the male: female ratio 24:5. Four samples of angiosarcoma and one of spindle cell haemangio-endothelioma were stained in parallel. All specimens were fixed in formalin, embedded in paraffin wax and processed routinely. Immunohistochemistry was carried out using an antibody directed against CD31 (JC70) and the monoclonal antibody P-GF.44C against TP. RESULTS: All biopsy specimens showed immunoexpression for TP. The spindle cell component stained more strongly than newly formed endothelium lined vessels and normal, resident vessels at a distance from the lesions. CONCLUSIONS: The strong immunoexpression of TP suggests up-regulation of TP and a role for TP in angiogensis in Kaposi sarcoma. The mechanism for the up-regulation of TP remains unknown, but viral infections may trigger it. The differential staining of the various cell components of Kaposi sarcoma also suggest that TP either plays a role in the differentiation and maturation of Kaposi sarcoma or is a reflection of such changes.
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- Blood C. H., Zetter B. R. Tumor interactions with the vasculature: angiogenesis and tumor metastasis. Biochim Biophys Acta. 1990 Jun 1;1032(1):89–118. doi: 10.1016/0304-419x(90)90014-r. [DOI] [PubMed] [Google Scholar]
- Cai J., Gill P. S., Masood R., Chandrasoma P., Jung B., Law R. E., Radka S. F. Oncostatin-M is an autocrine growth factor in Kaposi's sarcoma. Am J Pathol. 1994 Jul;145(1):74–79. [PMC free article] [PubMed] [Google Scholar]
- Dupin N., Grandadam M., Calvez V., Gorin I., Aubin J. T., Havard S., Lamy F., Leibowitch M., Huraux J. M., Escande J. P. Herpesvirus-like DNA sequences in patients with Mediterranean Kaposi's sarcoma. Lancet. 1995 Mar 25;345(8952):761–762. doi: 10.1016/s0140-6736(95)90642-8. [DOI] [PubMed] [Google Scholar]
- Ensoli B., Gendelman R., Markham P., Fiorelli V., Colombini S., Raffeld M., Cafaro A., Chang H. K., Brady J. N., Gallo R. C. Synergy between basic fibroblast growth factor and HIV-1 Tat protein in induction of Kaposi's sarcoma. Nature. 1994 Oct 20;371(6499):674–680. doi: 10.1038/371674a0. [DOI] [PubMed] [Google Scholar]
- Finnis C., Dodsworth N., Pollitt C. E., Carr G., Sleep D. Thymidine phosphorylase activity of platelet-derived endothelial cell growth factor is responsible for endothelial cell mitogenicity. Eur J Biochem. 1993 Feb 15;212(1):201–210. doi: 10.1111/j.1432-1033.1993.tb17651.x. [DOI] [PubMed] [Google Scholar]
- Fiorelli V., Gendelman R., Samaniego F., Markham P. D., Ensoli B. Cytokines from activated T cells induce normal endothelial cells to acquire the phenotypic and functional features of AIDS-Kaposi's sarcoma spindle cells. J Clin Invest. 1995 Apr;95(4):1723–1734. doi: 10.1172/JCI117849. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fox S. B., Moghaddam A., Westwood M., Turley H., Bicknell R., Gatter K. C., Harris A. L. Platelet-derived endothelial cell growth factor/thymidine phosphorylase expression in normal tissues: an immunohistochemical study. J Pathol. 1995 Jun;176(2):183–190. doi: 10.1002/path.1711760212. [DOI] [PubMed] [Google Scholar]
- Furukawa T., Yoshimura A., Sumizawa T., Haraguchi M., Akiyama S., Fukui K., Ishizawa M., Yamada Y. Angiogenic factor. Nature. 1992 Apr 23;356(6371):668–668. doi: 10.1038/356668a0. [DOI] [PubMed] [Google Scholar]
- Haraguchi M., Miyadera K., Uemura K., Sumizawa T., Furukawa T., Yamada K., Akiyama S., Yamada Y. Angiogenic activity of enzymes. Nature. 1994 Mar 17;368(6468):198–198. doi: 10.1038/368198a0. [DOI] [PubMed] [Google Scholar]
- Huang Y. Q., Li J. J., Kaplan M. H., Poiesz B., Katabira E., Zhang W. C., Feiner D., Friedman-Kien A. E. Human herpesvirus-like nucleic acid in various forms of Kaposi's sarcoma. Lancet. 1995 Mar 25;345(8952):759–761. doi: 10.1016/s0140-6736(95)90641-x. [DOI] [PubMed] [Google Scholar]
- Kempf W., Adams V., Pfaltz M., Briner J., Schmid M., Moos R., Hassam S. Human herpesvirus type 6 and cytomegalovirus in AIDS-associated Kaposi's sarcoma: no evidence for an etiological association. Hum Pathol. 1995 Aug;26(8):914–919. doi: 10.1016/0046-8177(95)90016-0. [DOI] [PubMed] [Google Scholar]
- Miles S. A., Rezai A. R., Salazar-González J. F., Vander Meyden M., Stevens R. H., Logan D. M., Mitsuyasu R. T., Taga T., Hirano T., Kishimoto T. AIDS Kaposi sarcoma-derived cells produce and respond to interleukin 6. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4068–4072. doi: 10.1073/pnas.87.11.4068. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moghaddam A., Zhang H. T., Fan T. P., Hu D. E., Lees V. C., Turley H., Fox S. B., Gatter K. C., Harris A. L., Bicknell R. Thymidine phosphorylase is angiogenic and promotes tumor growth. Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):998–1002. doi: 10.1073/pnas.92.4.998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reynolds K., Farzaneh F., Collins W. P., Campbell S., Bourne T. H., Lawton F., Moghaddam A., Harris A. L., Bicknell R. Association of ovarian malignancy with expression of platelet-derived endothelial cell growth factor. J Natl Cancer Inst. 1994 Aug 17;86(16):1234–1238. doi: 10.1093/jnci/86.16.1234. [DOI] [PubMed] [Google Scholar]
- Schwartz P. M., Barnett S. K., Reuveni H. Thymidine salvage changes with differentiation in human keratinocytes in vitro. J Invest Dermatol. 1991 Dec;97(6):1057–1060. doi: 10.1111/1523-1747.ep12492583. [DOI] [PubMed] [Google Scholar]
- Stürzl M., Roth W. K., Brockmeyer N. H., Zietz C., Speiser B., Hofschneider P. H. Expression of platelet-derived growth factor and its receptor in AIDS-related Kaposi sarcoma in vivo suggests paracrine and autocrine mechanisms of tumor maintenance. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7046–7050. doi: 10.1073/pnas.89.15.7046. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yoshimura A., Kuwazuru Y., Furukawa T., Yoshida H., Yamada K., Akiyama S. Purification and tissue distribution of human thymidine phosphorylase; high expression in lymphocytes, reticulocytes and tumors. Biochim Biophys Acta. 1990 Apr 23;1034(1):107–113. doi: 10.1016/0304-4165(90)90160-x. [DOI] [PubMed] [Google Scholar]

