Mucinous carcinomas of the breast, so-called
colloid carcinomas, exhibit better prognoses than their nonmucinous breast counterparts. This
biological difference exhibited by mucinous
breast carcinomas prompted us to examine the relationship of
mucin expression to
colloid carcinoma histogenesis. We studied 50
colloid carcinomas, 50 noncolloid
cancers, and 50 normal breasts by
hematoxylin-
eosin (H&E) and
Alcian blue staining,
mucin immunohistochemistry, in situ hybridization with a battery of MUC riboprobes, and ancillary digital image analysis. We observed
luminal mucin in normal ducts in 80% of
colloid carcinomas compared with 10% of noncolloid
carcinomas and 6% of normal breasts (P < .01). In the cases of
colloid carcinoma that showed
mucin-filled ducts,
luminal mucin was observed in 40% of the normal ducts and acini, 40% to 75% of the ducts involved by
hyperplasia, atypical ductal hyperplasia (ADH) and
ductal carcinoma in situ (
DCIS), respectively, and in 50% of the co-incidental areas of
cysts (
mucoceles), adenosis,
fibroadenoma, and
intraductal papilloma (P < .01). Immunohistochemistry showed that
colloid carcinomas showed strong MUC2 cytoplasmic immunoreactivity and decreased MUC1 immunoreactivity compared with noncolloid
carcinomas. In situ hybridization studies indicated fivefold increased MUC2 signals and twofold increased MUC5 signals within adjacent and remote normal epithelium in only the
colloid carcinoma cases (P < .01; P < .05). In these cases of
colloid carcinoma, these increased MUC2 and MUC5 signals were also observed in areas of
hyperplasia, ADH,
DCIS, and invasive
carcinoma. In contrast, the noncolloid
carcinomas showed fivefold increased MUC1 signals but no increases in MUC2 or MUC5. In mixed
colloid/noncolloid
carcinomas, the
colloid areas had identical
mucin expression patterns as the pure
colloid carcinomas, but there was a loss of MUC2 and MUC5 expression and a gain of MUC1 expression in the noncolloid areas that was therefore identical to the pattern observed in pure noncolloid
carcinoma. In this study, we conclude that the altered expression of
mucin so characteristic of
colloid carcinoma is also a field change present in adjacent and remote normal breast epithelium.