LOSS OF TYPE-IV COLLAGEN ALPHA-5 AND ALPHA-6 CHAINS IN HUMAN INVASIVEPROSTATE CARCINOMAS

Type IV collagen, a major component of basement membranes, is organize d in a network responsible for the mechanical resistance of the baseme nt membranes. It also plays a key role in epithelial tell adhesion to basement membranes. This study was designed to investigate the distrib ution of type IV collagen alpha-chains in normal, preneoplastic, and m alignant prostate basement membranes. For this purpose, immunohistoche mistry using specific antibodies raised against the different alpha-ch ains of type IV collagen was performed in eight normal samples, six pr ostatic intraepithelial neoplasia, and 20 malignant lesions of the pro state. Our results demonstrate the presence of the ''novel'' alpha 5 ( IV) and alpha 6 (IV) chains along with the ''classical'' alpha 1 (IV)/ alpha 2 (IV) chains in the basement membrane of the normal prostate gl and. The alpha 3 (IV) chain was never detected in any prostate specime n. Prostatic intraepithelial neoplasia showed a similar immunostaining pattern to that found in normal glands. In cancer gland basement memb ranes, we demonstrate for the first time a specific loss of the alpha 5 (IV) and alpha 6 (IV) chains, whereas the classical alpha 1 (IV) and alpha 2 (IV) chains were consistently exhibited. Additionally, type V II collagen colocalized with alpha 5 (IV) collagen chain, and these tw o proteins, which were always observed in normal and prostatic intraep ithelial neoplasia gland basement membranes, were lost in invasive car cinoma basement membranes. This observation raises questions about the possible association or cooperation between alpha 5 (IV)/alpha 6 (IV) chains and anchoring fibrils in prostate glands basement membrane.