Differential expression of fibronectin splice variants, oncofetal glycosylated fibronectin and laminin isoforms in nodular palmar fibromatosis

Abstract

The tissue formation process in nodular palmar fibromatosis (Morbus Dupuytren) was investigated by the demonstration of fibronectin splice variants (ED-A and ED-B fibronectin), de novo glycosylated fibronectin and laminin isoforms (A, M, B1, B2, s chains) in association to the proliferative activity (Ki-67 antigen) and the occurrence of myofibroblast phenotype (alpha-smooth muscle actin, desmin). The proliferative noduli of the fibromatosis were characterized by a diffuse immunostaining for alpha-smooth muscle actin, and single cells positive for desmin and the Ki-67 antigen. In contrast to the surrounding aponeurosis as extracellular matrix, components of the whole proliferative noduli were defined: ED-A, ED-B and de novo glycosylated fibronectin, B1 and B2 laminin chain, tenascin and collagen type IV. The demonstration of the A and M laminin chain was restricted to a few cells of the proliferative noduli. S laminin could be visualized in the majority of palmar aponeurotic fibroblasts. As revealed by mRNA, in situ hybridization a de novo synthesis of fibronectin could only be detected within proliferative noduli. There is a positive correlation between the myofibroblast phenotype formation, cellular proliferation and the occurrence of ED-A and ED-B containing fibronectin, as well as de novo glycosylated fibronectin in Dupuytren's disease. The ultrastructural irregularities of myofibroblastic basal lamina and the heterogeneity of the myofibroblast phenotype are equivalent to the variability of laminin isoform immunostaining.