Immunohistochemical and Clinical Characterization of the Basal-Like Subtype of Invasive Breast Carcinoma

Abstract

Purpose: Expression profiling studies classified breast carcinomas into estrogen receptor (ER)؉/luminal, normal breast-like, HER2 overexpressing, and basal-like groups, with the latter two associated with poor outcomes. Currently, there exist clinical assays that identify ER؉/luminal and HER2-overexpressing tumors, and we sought to develop a clinical assay for breast basal-like tumors.Experimental Design: To identify an immunohistochemical profile for breast basal-like tumors, we collected a series of known basal-like tumors and tested them for protein patterns that are characteristic of this subtype. Next, we examined the significance of these protein patterns using tissue microarrays and evaluated the prognostic significance of these findings.Results: Using a panel of 21 basal-like tumors, which was determined using gene expression profiles, we saw that this subtype was typically immunohistochemically negative for estrogen receptor and HER2 but positive for basal cytokeratins, HER1, and/or c-KIT. Using breast carcinoma tissue microarrays representing 930 patients with 17.4-year mean follow-up, basal cytokeratin expression was associated with low disease-specific survival. HER1 expression was observed in 54% of cases positive for basal cytokeratins (versus 11% of negative cases) and was associated with poor survival independent of nodal status and size. c-KIT expression was more common in basal-like tumors than in other breast cancers but did not influence prognosis.Conclusions: A panel of four antibodies (ER, HER1, HER2, and cytokeratin 5/6) can accurately identify basallike tumors using standard available clinical tools and shows high specificity. These studies show that many basal-like tumors express HER1, which suggests candidate drugs for evaluation in these patients.

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

“…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.…”

Distribution and significance of nerve growth factor receptor (NGFR/p75NTR) in normal, benign and malignant breast tissue

“…(II) Basal-like breast carcinomas As NGFR positivity was restricted to ER negative (11/11 cases) and 10 of these cases showed expression of basal-like immunohistochemical markers, the prognostic impact of NGFR was assessed in a second cohort of 37 high-grade ductal carcinomas classified as basal-like according to Nielsen et al 26 immunohistochemical panel. In this cohort, NGFR expression was observed in 38% of the cases (Figure 5e-h) and was associated with lack of lymph node metastasis at diagnosis (Po0.001).…”

“…There are several lines of evidence to suggest that highgrade breast carcinomas expressing basal/myoepithelial markers have distinct pathological features, expression profiles and, most importantly, clinical behaviour when compared to high-grade breast carcinomas devoid of basal-like differentiation. [23][24][25][26][27][28][29][30] The landmark studies of Perou et al 23 and Sorlie et al 24,25 revealed basal-like breast carcinomas to be more aggressive than oestrogen receptor (ER)-positive cancers, the former having significantly shorter disease-free and overall survival. Furthermore, recent data from our laboratory have suggested that basal tumours are heterogenous in terms of their molecular genetic profiles and that there might be a subgroup with a more favourable prognosis.…”

“…Here we analysed a large series of benign and preinvasive breast lesions, biphasic tumours, tumours with myoepithelial differentiation and two cohorts of patients with breast cancer: a cohort of 245 breast cancer patients treated with anthracycline-based adjuvant chemotherapy and 37 basal-like breast carcinomas as defined by the immunohistochemical panel proposed by Nielsen et al 26 …”