Expression of fibronectin isoforms in human breast tissue: Production of extra domain A+ extra domain B+ by cancer cells and extra domain A(+) by stromal cells

The expression of fibronectin (FN) isoforms including extra domain A (EDA) and extra domain B (EDB) segments, was investigated in 36 invasive ductal c arcinomas and 13 benign tumors of human breast tissues by in situ hybridiza tion using probes specific to alternative splicing sites. Signals for the c onstant region of FN mRNA in cancer cells were found in 53% of the invasive ductal carcinomas. The EDA(+) and EDB+ mRNA signals were found in 47% and 33%, respectively. Stromal cells expressing FN, EDA(+) and EDB+ mRNA signal s were present in 100%, 69% and 14% of cases, respectively, Expression of F N mRNAs by cancer cells was most frequent in intraductal lesions or large c ancer nests, and that by stromal cells was associated with desmoplastic are as. In representative cases, proportions of FN mRNA-positive cancer cells e xpressing EDA and EDB segments were 45% and 39%, respectively, signals for both being frequently found in the same cells. EDA(+) and EDB+ mRNA were la beled in 25% and 6% of the FN mRNA-positive stromal cells, a large proporti on thus being EDA(-)/EDB- FN, In conclusion, the splicing pattern of FN pre -mRNA is dependent an the cell type and histology of breast cancer tissues. The observed lack of expression in fibroadenomas and other benign conditio ns suggests a link with tumor progression.