Nodular
palmar fibromatosis is a self-limited proliferation of fibro-/myofibroblasts associated with
growth factor synthesis and abundant
fibronectin extracellular matrix deposition. bFGF and
TGF beta are potent modulators of fibro-/myofibroblast proliferation and differentiation. Moreover, in vitro investigations evidenced a
TGF beta 1-dependent regulation of alternative splicing of
fibronectin mRNA. To investigate a possible implication of these
growth factors in the tissue formation process of
palmar fibromatosis,
TGF beta 1/2 and bFGF synthesis, as well as
TGF beta 1/3 and bFGF tissue distribution, is demonstrated by
RNA in situ hybridization and/or immunohistochemistry in relation to myofibroblast phenotype development (alpha-smooth muscle actin,
desmin immunohistochemistry), expression of different
fibronectin isoforms (ED-A+, ED-B+ and oncofetal
glycosylated fibronectin immunohistochemistry,
fibronectin RNA in situ hybridization) and cellular activity (
cyclin RNA in situ hybridization, Ki-67 immunolabelling). The myofibroblast phenotype (alpha-smooth muscle actin,
desmin), the
growth factor synthesis (
TGF beta 1 and 2, bFGF),
fibronectin matrix synthesis (
RNA in situ hybridization with
cDNA) and ED-A+, ED-B+ and oncofetal
glycosylated fibronectin immunostaining are exclusively localized in the active proliferative nodules (Ki-67 immunolabelling and
cyclin mRNA demonstration). Whereas the
growth factor synthesis is restricted to the proliferative areas of the
fibromatosis only,
TGF beta 1,
TGF beta 3 and bFGF
proteins can also be detected immunohistochemically with a lower intensity in the surrounding aponeurotic tissue. The spatial correlation of myofibroblast phenotype,
TGF beta and bFGF synthesis and the occurrence of the oncofetal molecular
fibronectin variants (ED-B+ and oncofetal
glycosylated fibronectin) in the active proliferative
fibromatosis nodules suggests a pathogentic role of these
growth factors and matrix components in the tumorous tissue formation process. The presence of the bFGF and
TGF beta 1/3
proteins in fibroblasts neighbouring the proliferative nodules may point to a recruitment of quiescent aponeurotic fibroblasts in the fibromatous tissue formation process.