Evidence for a Multiclonal Origin of Multicentric Advanced Lesions of Kaposi Sarcoma

Abstract

Although some tumor KS lesions were monoclonal expansions of HHV-8-infected spindle cells, most advanced lesions were oligoclonal proliferations. Furthermore, individual KS disseminated tumor skin lesions were found to represent distinct expansions of HHV-8-infected spindle cells. Thus, our results suggest that KS lesions, especially in patients with advanced skin tumors, are reactive proliferations rather than true malignancies with metastatic dissemination.

KSHV and the pathogenesis of Kaposi sarcoma: listening to human biology and medicine

“…But this designation is not strictly correct, and its continuing use largely reflects the absence of an alternative word to denote their centrality to KS pathogenesis. In fact, spindle cells have few properties in common with malignantly transformed cells - they usually (27,28) (though not invariably; ref. 29) lack clonality, even in welldeveloped lesions.…”

“…Interestingly, in AIDS-KS, the temporal pattern of occurrence of multifocal lesions is often not consistent with spread from a primary lesion, but rather suggests independent occurrences (multicentricity) (33). This inference has been supported by molecular analysis of KSHV genomes from KS lesions, which has affirmed that different lesions from the same patient often harbor genomes of differing terminal structure, suggesting they arose from independent infection events (28).…”

KSHV Paracrine Effects on Tumorigenesis

“…The largest study was performed in 2007 on 62 biopsies. In order to investigate the cellular clonality of KS lesions, the authors determined the size heterogeneity of the KSHV-fused terminal repeat region (Duprez et al, 2007). The authors revealed in 59 cases a clonal pattern.…”

Kaposi sarcoma

“…4 It is interesting to note that although some KS lesions are monoclonal expansions of HHV-8-infected spindle cells, more advanced lesions appear to represent distinct oligoclonal proliferations. 6 It is well known that KS is usually more frequent, widely disseminated, and presents more aggressively in AIDS than in other immunodeficiency states. Additional factors in this setting, such as the HIV-1 Tat protein, certainly stoke the fire.…”