HETEROGENEOUS EXPRESSION OF THE LIPOCALIN NGAL IN PRIMARY BREAST CANCERS

We have previously shown that neo oncogene-initiated rat mammary carci nomas uniquely over-express neu-related lipocalin (NRL), a member of t he calycin protein superfamily. Here, we characterize the putative hum an homolog of NRL, neutrophil gelatinase-associated lipocalin (NGAL). ngal gene expression was found at moderate levels in only 2 of 17 huma n tissues examined, breast and lung. When breast cancers were examined for NGAL mRNA and protein levels, they were found to exhibit heteroge neous expression. NGAL levels varied in these tumors from undetectable to exceeding those in normal breast parenchyma. Immuno-histochemical analysis confirmed the presence of NGAL within breast carcinoma cells but detected only low levels of this protein in normal ductal epitheli um. in contrast, large amounts of the protein were localized to the lu men of normal breast ducts in the vicinity of NGAL-expressing tumors. Interestingly, unlike NRL in rat mammary carcinomas, no significant as sociation between NGAL expression and HER-2/neu activation was found i n human breast tumors. In contrast, a significant correlation between NGAL expression in breast cancer was found with several other markers of poor prognosis, including estrogen and progesterone receptor-negati ve status and high proliferation (S-phase fraction). NGAL levels were stratified as high or low in breast cancers from a cohort of nodeposit ive patients with known outcome. No significant association between NG AL expression and disease-free or overall survival was observed. (C) 1 998 Wiley-Liss, Inc.