The expression of the
estramustine/
estromustine-
binding protein (
EMBP) in human
mammary cancer and
malignant melanoma was examined by immunochemical methods and compared with that in endometrial and
ovarian cancers. By RIA measurements,
EMBP was detected in 6/17
mammary cancers (range 11.3-2,660 ng/g tissue) and 2/3
malignant melanomas (618 and 1,240 ng/g), whereas endometrial (n = 6) and ovarian (n = 3)
cancers exhibited non-detectable levels. In
breast cancer,
EMBP-expressing tumours were all
estrogen receptor-negative, suggesting an inverse correlation between
EMBP and
hormone responsiveness of the tumour. Biochemical characterization revealed properties of
EMBP in mammary tumours and
melanomas almost identical to those for
EMBP purified from rat ventral prostate: i.e. surface-charge distribution by
Mono Q/FPLC ion-exchange chromatography, a molecular weight of 50,000 by gel filtration, and a subunit composition by Western blot analysis under denaturing conditions. Finally, the
EMBP immunoreactivity was confined to the cytoplasm of malignant cells in
breast cancer and
melanoma sections by immunohistochemical examination. This is the first study that demonstrates
EMBP in
mammary cancer and
malignant melanoma. Our findings suggest that a mechanism for selective uptake of cytotoxic
estramustine and
estromustine is prevailing in these
malignancies and that monitoring of
EMBP in biopsy samples will be of value in defining patients who may benefit from
Estracyt treatment.