Distribution of oncofetal fibronectin isoforms in normal, hyperplastic and neoplastic human breast tissues

Abstract

Two different oncofetal fibronectins (FN) have been reported: one, generated by O-glycosylation in the splicing region IIICS that is recognized by monoclonal antibody (MAb) FDC-6, and another, recognized by MAb BC-I, generated by the alternative splicing of the FN pre-mRNA which includes an extra type-III repeat called ED-B. Using these and 2 other MAbs (IST-4 which recognizes all different FN isoforms and IST-6 which recognizes only the FN molecules that do not include the ED-B sequence) we have immunohistochemically studied 171 normal, hyperplastic and neoplastic breast-tissue specimens. Although all normal specimens reacted strongly with MAbs IST-4 and IST-6, they did not show the presence of oncofetal FNs as established by the use of BC-1 and FDC-6. In contrast, out of the 97 cases of invasive ductal carcinomas studied, 90 (93%) and 96 (99%) reacted positively with BC-I and FDC-6, respectively, the reaction being observed in the tumoral stroma connective tissue and in tumoral vessels. Furthermore, invasive lobular carcinoma showed less intense and less frequent staining with BC-1 and FDC-6 (10 and 11 out of 14, respectively). We found differences in the distribution of the 2 oncofetal fibronectin isoforms within the same specimens. The most remarkable difference was observed in the tumoral vessels: in invasive ductal carcinoma MAb BC-1 revealed a positive reaction with vessels in 78% of cases while FDC-6 showed such a reaction in only 59% of cases.