Immunohistochemical demonstration of the gamma2 chain of laminin-5 in urinary bladder urothelial carcinoma. Impact for diagnosis and prognosis.

The heterotrimeric molecule laminin-5 (Ln-5) represents a main protein of the epithelial adhesions complex. It links the basement membrane (BM) with the hemidesmosomes of the basal urothelial cells. The study was aimed to evaluate invasion associated changes of the epithelial adhesion complex in urothelial carcinoma (UC) monitored by immunohistochemical demonstration of the Ln-5 gamma2 chain. For correlation to UC phenotype and patients outcome, a semiquantitative immunohistochemical analysis of 100 routinely processed paraffin embedded samples (non-invasive and invasive UC) using the antibody D4B5 specific for the Ln-5 gamma2 chain was performed. An increased risk of death is associated with an increased Ln-5 loss from BM (P=0.001), an increase of stroma deposition (P=0.001), as well as an increase of cellular retention of Ln-5 protein (P=0.001) (Kruskal-Wallis test). As shown in multivariate analysis, in addition to tumor stage the cellular retention of Ln-5 is the most important prognostic parameter. In consequence, the modulation of Ln-5 is recommended as a diagnostic marker of invasive UC phenotype.