Identification of a clonal form of HIV in early Kaposi's sarcoma: evidence for a novel model of oncogenesis, "sequential neoplasia".
We recently reported clonal human immunodeficiency virus (HIV involvement in four acquired immune deficiency syndrome (AIDS)-associated non-B-cell lymphoproliferations. In three of these cases HIV expression was localized to tumor-associated macrophages. Because one of the cases had a major component involved in angioproliferation, we speculated that some form of Kaposi's sarcoma (KS), which also has a major component of angioproliferation, might be involved clonally with HIV. The current study is an evaluation of four cases of KS and control tissues taken from four patients who died with complications of HIV disease. With use of the inverse polymerase chain reaction technique to identify clonal forms of HIV, a clonal form of HIV was found in one of four KS cases. The HIV-positive tumor was an early KS lesion of the bowel, and uninvolved bowel from the same patient showed no clonal HIV. Immunohistochemical analysis demonstrated the presence of prominent HIV-expressing macrophages that also coexpressed high levels of HIV tat, basic fibroblast growth factor, and interleukin-6. These data provide evidence for a pathogenic process termed "sequential neoplasia," wherein a clonal macrophage provides a growth factor milieu stimulating the proliferation of a responder cell population that ultimately becomes autonomous. In the current case, the macrophages expressing HIV were located adjacent to the KS tumor tissue and were found to be producing known KS growth factors. The absence of finding clonal HIV in three more advanced KS lesions suggests that the clonal macrophage may be required only for early pathogenesis and that sequential neoplastic changes occurring in the endothelial cells gave rise to autonomous KS.(ABSTRACT TRUNCATED AT 250 WORDS)
McGrath
M S
MS
Department of Laboratory Medicine, San Francisco General Hospital, CA 94110.
Shiramizu
B T
BT
Herndier
B G
BG
D001483:Base Sequence; D017931:DNA Primers; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D015756:Genes, tat / Q000235:genetics*; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis; D007414:Intestinal Neoplasms / Q000737:chemistry / Q000235:genetics*; D007422:Intestines / Q000737:chemistry; D008264:Macrophages / Q000821:virology; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D009857:Oncogenes / Q000235:genetics*; D012514:Sarcoma, Kaposi / Q000737:chemistry / Q000235:genetics*; D016662:Virus Integration / Q000235:genetics
D017931:DNA Primers; D016655:HIV Core Protein p24; D015850:Interleukin-6; D015345:Oligonucleotide Probes; D016222:Fibroblast Growth Factor 2