FIBRONECTIN ISOFORMS ARE DIFFERENTIALLY EXPRESSED IN NORMAL AND ADENOMATOUS HUMAN ANTERIOR PITUITARIES

The expression of fibronectin (FN) isoforms containing the extradomain s A and B (ED-A(+) and ED-B+ FNs) as well as a differentially O-glycos ylated oncofetal form of the protein (onf-FN) was investigated in 6 no rmal human anterior pituitaries and 25 human pituitary adenomas. In no rmal tissue, immunohistochemical experiments showed the presence of FN molecules lacking the extradomains A and B (ED-A(-) and ED-B- FNs) wi thout onf-FN immunoreactivity. These proteins were localized in the co nnective tissue compartment and especially in the vessel walls. Analys is of FN mRNA demonstrated an in situ synthesis of ED-A(-) and ED-B- F Ns in the normal anterior pituitary, By contrast, in the adenomas, imm unoreactivity for ED-A(+) FN was observed in all cases, ED-B+ and onf- FN immunoreactivities were observed in 14 and 8 adenomas, respectively , regardless of the type, grade or invasiveness of the adenomas. ED-A( +) FN mRNA was expressed in all adenomas studied, and ED-B+ FN mRNA wa s present in ED-B+ immunoreactive cases only. In pituitary adenomas, t hese 3 forms of FN were specifically associated with the endothelium a nd vascular smooth-muscle cells. Our results demonstrate that the proc esses of remodelling of the connective tissue compartment that occur i n adenoma angiogenesis are associated with pre- and post-translational alterations of FN synthesis leading to the expression of ED-A(+), ED- B+ and oncofetal FNs. (C) 1995 Wiley-Liss, Inc.