Immunohistologic analysis of estrogen receptor expression in breast carcinoma precursor lesions

The growth of invasive breast carcinoma is facilitated by abnormal expression of estrogen receptor (ER), however, the status of ER during disease histogenesis is poorly defined. The extent of ER immunostaining (expressed as percentage of positive cells) was semiquantitated in the invasive (ICA) and corresponding in situ (CIS) components of 50 formalin- fixed, paraffin-embedded breast carcinomas and then compared to staining in normal terminal duct lobular units (TDLU) or hyperplastic lesions (if present) in the same tissue sections. Morphologically normal TDLUs from most cases (61%) exhibited ER staining in 11-30% of epithelial cells; only 10% of the cases had TDLUs demonstrating immunoreactivity in more than 50% of cells. In contrast, 80% of the hyperplastic lesions showed ER staining in more than 30% of epithelial cells, with 44% demonstrating immunoreactivity in more than 50% of epithelial cell nuclei (p = 0.01, chi-square test). Although most in situ carcinomas showed even more extensive ER staining than hyperplasias (>70% of cells were positive in 50% of cases), a significant subset (28%) of CIS exhibited staining in less than 10% of cells (p = 0.002, chi-square test). Invasive carcinomas were less often extensively immunoreactive (i.e., >50% of cells positive) than CIS (32% versus 58% for CIS) and there were five cases (10%) in which the CIS component was ER positive but the invasive component was ER negative. Finally, ER-positive carcinomas were significantly more often accompanied by extensive CIS and/or proliferative breast disease (p = 0.007 and 0.003, respectively). The divergent levels of ER expression observed between premalignant, preinvasive, and invasive lesions suggests that inappropriate regulation of hormone receptors may be a factor that promotes early growth or progression in breast neoplasia, and ER-positive breast carcinomas are characterized by a different, possibly lengthier, histogenesis than ER-negative malignancies with a greater frequency of background hyperplastic lesions and a larger preinvasive component.