Expression and prognostic value of lactoferrin mRNA isoforms in human breast cancer

We investigated the expression levels of human lactoferrin (Lf), a steroid hormone-inducible gene product the expression of which is often altered during oncogenesis, and of Delta-lactoferrin (DeltaLf), its alternative isoform, which has been shown to be absent from tumor cell lines in commonly used human breast epithelial cell lines, using semiquantitative RT-PCR. Both mRNAs were detected but with levels of expression lower than those found in normal breast epithelial cells. This downregulation was much more visible for DeltaLf since its expression was either significantly diminished (BT-20, MCF-7 cell lines) or practically absent (MDA-MB-231, T-47D, HBL 100 cell lines). In order to determine whether Lf gene products are useful prognosic tools, we further analyzed their expression levels in 99 primary breast cancer biopsies. DeltaLf transcripts were found in all of the samples, whereas Lf transcripts were found in 88% of them. Lf and DeltaLf expression levels were positively correlated (p = 0.003). Lf expression was related to tumor type with a higher recovery in lobular-type tumors (p = 0.04). DeltaLf expression was related to the histoprognostic grading (p = 0.02). In univariate analyses, DeltaLf and Lf expressions were prognosis parameters, high concentrations being associated with a longer overall survival. (C) 2004 Wiley-Liss, Inc.