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.