Abnormalities in mucin-type glycoprotein expression have been documented in
a variety of cancers, identifying these molecules as targets for immunolog
ically based therapies and prognostic/diagnostic assays. We examined the ex
pression of the membrane-bound MUC1 mucin in normal, histologically atypica
l, and neoplastic lung to determine its potential contribution to lung carc
inogenesis. Zn vivo, intense MUC1 immunoreactivity was present in normal ty
pe II pneumocytes as well as In a range of atypical lesions derived from ty
pe II cells and >60% of primary and metastatic non-small cell lung cancers.
Expression was not associated with altered survival, although it was highl
y correlated with the adenocarcinoma histology. A carcinogenesis model usin
g 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone-exposed hamsters reve
aled that MUC1 mRNA increased prior to the histological appearance of tumor
s. In vitro studies using MUC1 expressing non-small cell lung cancer cell l
ines revealed that differentiation away from a type II cell lineage was ass
ociated with dramatic down-regulation of MUC1. We propose that MUC1 is a po
werful new marker for the type II pneumocyte cell lineage that allows us to
follow the type II pneumocyte lineage during the process of lung carcinoge
nesis.