Basement Membrane and Connective Tissue Proteins in Early Lesions of Kaposi's Sarcoma Associated with AIDS

Abstract

Nearly one-third of all young homosexual men diagnosed as having acquired immune-deficiency syndrome (AIDS) develop a disseminated form of dermal Kaposi's sarcoma (KS). Although the histogenesis of KS cells is unclear, certain evidence suggests that the aberrant cells are of endothelial derivation. We have examined the presence and distribution of connective tissue-specific and basement membrane-specific macromolecules by indirect immunofluorescence and immunoperoxidase staining of frozen sections in early cutaneous lesions of KS from individuals with AIDS. The KS cells typically line the spaces between collagen bundles of the reticular dermis. When stained for the connective tissue-specific glycoprotein fibronectin, all Kaposi's sarcoma lesions showed an intense staining pattern, revealing a complex array of linear deposits of antigen that outlined the exterior surface of the collagen bundles. Antibodies to laminin and type IV collagen, both basement membrane-specific macromolecules, produced an intense staining pattern similar to that found with the anti-fibronectin antiserum, indicating that all 3 antigens are closely codistributed. In contrast, antibodies to type I collagen, the major collagen of the dermis, uniformly stained the collagen bundles in the KS lesions and in the normal control skin. Antiserum to factor VIII-associated antigen, an antigen specific to blood vascular endothelium, frequently stained the KS lesions but the staining pattern was diffuse and of variable intensity. The results suggest that KS cells are derived from the endothelium of the blood microvasculature and maintain their secretory phenotype of secreting basement membrane-specific macromolecules.

Ultrastructural findings in oral Kaposi's sarcoma (AIDS)

“…The oecurrence of WPB is increased in endothelial cells of rapidly proliferating capillaries during wound healing as well as tumor angio-Ultrastrttctural findings in oral KS (AIDS) 377 genesis, and seems to be a marker lor endothelial activity (23). Endothelial cells in early lesions of oral KS as well as of other sites (20) showed partly interrupted basal tnembranes, while around spindle-shaped cells of late KSlesions no basal tnetnbranes were identified. Basal membranes are considered to be extracellular tnatrices, separating epitfielia and endothelia frotn underlying connective tissue, to play an important role in blood vessel permeability, in endothelial cell attachment and vascular tissue organisation, and to act as a barrier to cellular tnigration (25).…”

“…Endothelial cells with enlarged, pleomorphic nuclei, apparently thickened capillary walls and desintegration of basal membranes were considered to be morphological criteria for early neoplastic growth (5,20). While eells lining proliferating vessels showed characteristics of endothelial eells like WPB, small tight-junctions or desmosomes and fragments of basal membranes, spindle-shaped tumor eells did not possess these ultrastructural markers of endothelial cells (7,8).…”

“…Fragmentation of the basal metnbrane is a valuable tnarker indieating mictoinva-sion of a eatcinoma //; silu (18). Itnmunohistochetnical studies revealed, that spindle-shaped cells during late stages of KS seetete oecasionally diffuse interstitial deposits of basal membrane specific ptoteins, but loose their ability to interact with each other, to form regular vascular structures with attachment to adjacent cells and basal metnbtane (20). Whether the loss of basal inembrane integrity around tumor vessel spaces is due to enzymatic digestion by penettating tumor cells, as observed in invading carcinotnas, is not yet established (18).…”

Ultrastructural findings in clinically uninvolved oral mucosa of patients with HIV infection

“…Part!y interrupted basa! membranes, !eading to extravasation of erythrocytes, have been found around endothelial cells in early KS lesions (6,14,18) as well as in chnically uninvolved skin in AIDS patients(ll). Simi!ar phenomena were seen in this study in biopsies of c!inica!…”

Cutaneous Manifestations of the Acquired Immunodeficiency Syndrome

“…Biopsy shows the typical histologic features of moiluscum contagiosum (Figs. 6,7,8). A relationship between these warts and the deficient cell-mediated immunity has been postulated.'''…”