EVIDENCE FOR MULTICLONALITY IN MULTICENTRIC KAPOSIS-SARCOMA

Kaposi's sarcoma (KS) develops in a variety of clinical states and is the most common tumor seen in patients with HIV-1 infection. KS develo ps as a multifocal mucocutaneous disease with subsequent spread to vis ceral organs, and it has been argued to be a benign proliferation caus ed by its multifocality at initial presentation, lack of aneuploidy, a nd spontaneous regression upon withdrawal of immunosuppressive agents in iatrogenically induced disease. We wished to determine whether KS l esions are clonal, indicative of a true neoplasm, Also, we tested whet her multifocal KS lesions are clonally related, derived from a common progenitor cell or of independent cellular origin. We studied the X-ch romosome inactivation pattern of the human androgen receptor gene in t umor biopsies of women with KS. This procedure tests for the clonality of a tissue specimen, a hallmark of neoplasia. Each specimen was micr odissected to minimize normal cell contamination, Of 12 evaluable case s, 10 were HIV-seropositive and 2 were HIV-seronegative. Twenty-four b iopsies from the 12 patients were examined. Five cases were consistent with individual KS lesions being clonal. In two cases, multiple KS sp ecimens derived from the individual patients had different androgen re ceptor alleles inactivated, proving unequivocally that these KS lesion s arose independently from distinct transformed cells. In seven cases, only a polyclonal pattern of inactivation was observed, whereas two o thers had tumor areas of both clonal and polyclonal inactivation patte rns. These findings suggest that KS can be a clonal neoplasm, and in s ome of the cases multiple KS lesions in a given patient can arise from independent cellular origins and acquire clonal characteristics. The polyclonal inactivation pattern observed in other KS lesions may repre sent a premalignant stage or false negative results.