Sequential neoplasia: a novel theory of pathogenesis for HIV-associated lymphoma and Kaposi's sarcoma (Meeting abstract).

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

Sequential neoplasia: a novel theory of pathogenesis for HIV-associated lymphoma and Kaposi's sarcoma (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 36:A1181 1995. Unique Identifier : AIDSLINE ICDB/95608958
Herndier BG; Shiramizu BT; McGrath MS; Univ. of California San Francisco, San Francisco, CA 94143

Abstract: In Cancer Research (Shiramizu et al, 54:2069-72, 1994) we presented 4 HIV-associated lymphoproliferations with nonrandom clonal integration of the retrovirus in the fur gene of the fur fps/fes complex on chromosome 15. Clonal integration of HIV has now been demonstrated in 15 HIV-associated lymphoproliferations (3 lymphomas, 3 cases of AILD, 2 cases of atypical Hodgkin's disease, 6 cutaneous lymphomas, 1 malignant B-cell effusion) and an early KS lesion of the bowel. The method used is inverse polymerase chain reaction (IPCR) featuring Sau3a digestion, T4 ligase circularization, and PCR with back-to-back HIV-LTR primers designed to capture flanking host genome at the integration site. Integration is detectable by IPCR when greater than 5% of the tumor cells are involved. A common theme in the 16 lesions with positive HIV-LTR IPCR is the presence of numerous tumor macrophages. In several tumors HIV viral proteins were associated with macrophages and using PCR in situ hybridization the HIV-LTR was localized to macrophages. From the IPCR results and cell culture studies, we hypothesize the clonal HIV integration in macrophages (HIV-Mphi) would be the first neoplastic steD. The HIV-Mphis serve as a paracrine source of cytokines for lymphoid hyperplasia. Development of autonomous cytokine growth and/or further genetic changes in the lymphoid compartment are features of progression to a second neoplasm--a frank monoclonal lymphoma. Sequential neoplasias may lead to better understanding of the biology, epidemiology and future treatment of HIV-associated malignancies.

Keywords: DNA Primers Human HIV Infections/*COMPLICATIONS HIV Long Terminal Repeat In Situ Hybridization Lymphoma/COMPLICATIONS/*PHYSIOPATHOLOGY Macrophages/VIROLOGY Polymerase Chain Reaction Sarcoma, Kaposi's/COMPLICATIONS/*PHYSIOPATHOLOGY Virus Integration ABSTRACT
950930
M9591328

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