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

Abstract

Microarray profiling of invasive breast carcinomas has identified five distinct subtypes of tumors (luminal A, luminal B, normal breast-like, HER2 overexpressing, and basal-like) that are associated with different clinical outcomes. The basal-like subtype is associated with poor clinical outcomes and is the subtype observed in BRCA1-related breast cancers. The aim of this study was to characterize the histologic and immunophenotypic properties of breast basal-like carcinomas that were first positively identified using DNA microarray analysis. Detailed histologic review was performed on 56 tumors with known microarray profiles (23 basal-like, 23 luminal, and 12 HER2 þ ). Immunohistochemistry for estrogen receptor (ER), HER2, EGFR, smooth muscle actin (SMA), p63, CD10, cytokeratin 5/6, cytokeratin 8/18, and vimentin was performed on 18 basal-like, 16 luminal, and 12 HER2 þ tumors. The basal-like tumors were grade 3 ductal/NOS (21/23) or metaplastic (2/23) carcinomas that frequently showed geographic necrosis (17/23), a pushing border of invasion (14/23), and a stromal lymphocytic response (13/23). Most basal-like tumors showed immunoreactivity for vimentin (17/18), luminal cytokeratin 8/18 (15/18), EGFR (13/18), and cytokeratin 5/6 (11/18), while positivity for the myoepithelial markers SMA (4/18), p63 (4/18) and CD10 (2/18) was infrequent. All basal-like tumors tested were ERÀ and HER2À. Morphologic features significantly associated with the basal-like subtype included markedly elevated mitotic count (Po0.0001), geographic tumor necrosis (P ¼ 0.0003), pushing margin of invasion (P ¼ 0.0001), and stromal lymphocytic response (P ¼ 0.01). The most consistent immunophenotype seen in the basal-like tumors was negativity for ER and HER2, and positivity for vimentin, EGFR, cytokeratin 8/18, and cytokeratin 5/6. The infrequent expression of myoepithelial markers in basal-like carcinomas does not support a direct myoepithelial cell derivation of these tumors. These findings should further assist in the identification of basal-like carcinomas in clinical specimens, facilitating treatment and epidemiologic studies of this tumor subtype.

Expression of basal keratins and vimentin in breast cancers of young women correlates with adverse pathologic parameters

“…In particular, basal-like breast cancers defined using expression profiling are found to be negative for ER and c-erbB2, and positive for vimentin, EGFR, cytokeratin 8/18, and cytokeratin 5/6 on immunohistochemistry. 36 Our results reinforce the association between these immunohistochemical markers in our series of breast cancers in young women, and also corroborate our previous finding of conservation of molecular subtypes in women of Asian ethnicity. 37 In summary, our study confirms the association of basal cytokeratins and vimentin with adverse pathologic features in our series of young women with breast cancer, with our in vitro work lending support to our conclusions.…”

“…A similar trend has been observed in many recent reports which showed that basal-like tumors expressed EGFR (HER1). 28,31,32 Coexpression of HER-1, HER-2 and HER-3 was demonstrated to have a negative synergistic effect on patient outcome. 33 These studies further showed that expression of basal cytokeratins and vimentin are associated with more aggressive tumor features and poorer disease prognosis.…”

Basal phenotype of ductal carcinoma in situ: recognition and immunohistologic profile

“…Our morphologic review, and immunohistochemical stains revealed almost identical findings as reported by Livasy et al 5 The tumors were all high grade (Nottingham score 9/9), with variable geographic necrosis, moderate to good microscopic circumscription and significant lymphoid inflammatory cell infiltrates The tumors were also positive for EGFR (94%) and vimentin (100%). Staining for other sensitive and specific myoepithelial markers (SMA, C-kit, p63) was seen in less than 50% of cases, which indicates that these tumors demonstrate a partial myoepithelial phenotype.…”

“…Our study confirms and extends the previously reported findings of the basal-like carcinoma immunophenotype. [5][6][7][8]10 In addition, we demonstrate the presence of in situ carcinoma as the likely precursor lesion for invasive basal-like carcinoma.…”

“…5 The characteristic immunohistologic phenotype of these tumors is the 'triple negative' receptors of estrogen, progesterone and HER-2/neu, while expressing keratins CK5/6, CK14, CK17, vimentin and HER-1. [5][6][7][8][9][10][11] While the invasive basal-like neoplasms are reasonably well characterized morphologically and immunohistochemically, there is little data about the precursor lesion(s) for the entity.…”