Estrogen receptor-negative breast carcinomas: a review of morphology and immunophenotypical analysis

Abstract

Estrogen receptor (ER)-negative breast cancers are a group of tumors with poor prognosis and fewer cancer prevention and treatment strategies compared to ER-positive tumors. The aim of this study was to assess the morphological characteristics and immunohistochemical profile of ER-negative tumors and thus to understand the biological behavior and unique nature. In total, 291 consecutive ER-negative cases available from our primary breast cancer series were examined. Hematoxylin-and eosin-stained sections of all the cases were studied for several morphological parameters and their immunophenotype profile. These findings were correlated with patient and tumor characteristics and survival data. ER-negative tumors constituted 30% of the primary operable breast cancer series. The majority of tumors were grade 3 (94%) and the commonest histological types were ductal/no specific type (85%), and atypical medullary carcinoma (8%). High-grade comedo-type necrosis, lymphoid stroma, central necrosis/fibrosis and pushing margins were the most common morphological features. The presence of a pushing margin showed a significant relation to androgen receptor negativity, absence of epidermal growth factor receptor expression and negative lymph nodes. Lymphoid stroma and comedo-necrosis correlated with higher tumor grade. ER-negative breast cancers are a distinct group of tumors with several common morphological features. Grade 3 histology, pushing margin, lymphoid stroma, comedo-type necrosis and central fibrosis/necrosis are the dominant morphological findings. The presence of a pushing margin appears to have a significant correlation with negative lymph node status. ER-negative tumors show a higher expression of p53, CerbB2 and epidermal growth factor receptor compared to ER-positive breast cancer. These unique features support the concept that ER-negative tumors are a morphologically and phenotypically distinct entity and provide a rationale for the study and use of newer promising agents in the treatment of ER-negative breast cancer.

Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma

“…Both subtypes share histologic features that have been previously reported as characteristic of ERÀ breast carcinomas. 20 These features include grade 3 histology and geographic necrosis. Although there are some histologic features that appear to be distinctive of basal-like carcinomas, immunohistochemical studies are clearly needed for subtyping of high-grade breast carcinomas.…”

Expression of basal and luminal cytokeratins in breast cancer and their correlation with clinicopathological prognostic variables

“…[5] A signiÞ cant amount of data exists concerning the histological characteristics of ER-negative tumors and the immunohistochemical patterns of expression of nonluminal cell markers (like SMA, p63 and vimentin) in breast carcinomas. The precise relationship between these features and basal-like tumors, however, is not known because the only reliable method to identify basal-like tumors is by microarray analysis.…”

“…Conversely, ERnegative tumors are more likely to be of higher histological grade, and the patients more likely to have a decrease in survival depending on age and lymph node status. [5] Normal breast ducts contain at least 3 types of epithelial cells: luminal (glandular) cells, basal/ myoepithelial cells and stem cells. Myoepithelial and luminal epithelia can be distinguished by their different cytokeratin expression patterns.…”

“…Myoepithelial cells typically express cytokeratin 5/6 and cytokeratin 17, while luminal cells typically express cytokeratins 8 and 18. [5] A small fraction of breast cancers express CK5 together with its major partners CK14 and CK17. [6] Basal-like tumors express many of the genes characteristic of breast basal epithelial cells.…”

Comparison of basal-like triple-negative breast cancer defined by morphology, immunohistochemistry and transcriptional profiles

“…18,20 In particular, large zones of geographic necrosis, frequent apoptotic cells, stromal lymphocytic infiltrates and scanty stromal content are characteristic. 21 Occasionally, these tumors also contain areas of spindle cell and squamous metaplasia. 14,22 From a morphologic point of view, basal-like breast carcinomas are clearly a heterogeneous group of cancers, including medullary, metaplastic and spindle cell, myoepithelial and adenoid cystic tumors.…”