Defective expression of basement membrane-associated C3d,g in papulonodular basal cell carcinomas

Abstract

Recent studies in our laboratory have shown that C3d,g, a 41,000-Da fragment of the third component of complement, is present along the base of the lamina densa and in the sublamina densa region of normal human epidermal basement membrane, but absent from the skin of a patient with congenital C3 deficiency. In studies of human skin, papulonodular basal cell carcinomas have served as a useful model for the investigation of various basement membrane antigens and matrix proteins. To further investigate the presence of C3d,g within epidermal basement membrane as well as examine its relationship with other known basement membrane constituents, we have analyzed serial sections of ten papulonodular basal cell carcinomas by light and immunofluorescence microscopy. In these studies, C3d,g was either absent (N = 9) or minimumly detectable (N = 1) in tumor nest basement membranes. While bullous pemphigoid and KF-1 antigens were absent (N = 6 and N = 3, respectively) or significantly decreased (N = 4 and N = 7, respectively), epidermolysis bullosa acquisita antigen was routinely present though somewhat (N = 3) or moderately decreased (N = 3).Laminin and type IV collagen were expressed normally in all tumor nest basement membranes. All constituents, including C3d,g, were present in adjacent normal epidermal basement membrane of these tumor samples. This study has demonstrated antigenic alterations within each ultrastructural subregion of papulonodular basal cell carcinoma tumor nest basement membranes by identifying the virtual absence of C3d,g (sublamina densa) as well as a significant reduction in KF-1 (lamina densa) and bullous pemphigoid (lamina lucida) antigens. Moreover, the presence of laminin, type IV collagen, and epidermolysis bullosa acquisita antigen in tumor nest basement membranes suggests that these particular constituents neither cleave C3 nor act as essential binding sites for passive incorporation of this complement component in epidermal basement membrane. These studies give additional support to the hypothesis that C3d,g is a previously unrecognized constituent of normal epidermal basement membrane and does not represent passive incorporation of circulating C3 at this site in human skin.