Immunohistochemical heterogeneity of breast carcinomas negative for estrogen receptors, progesterone receptors and Her2/neu (basal-like breast carcinomas)

Abstract

Basal breast carcinomas triple negative for estrogen receptors, progesterone receptors and Her2/neu breast carcinomas are more aggressive than conventional neoplasms. We studied 64 cases with immunohistochemistry, using 23 antibodies, to characterize diverse pathological pathways. A basal cytokeratin was identified in 81% of tumors and vimentin was identified in 55%. The mean Ki67 index was 46% (range, 10-90%). Coincident expression of p50 and p65, which suggests an active nuclear factor-jB factor, was present in 13% of neoplasms. Epithelial growth factor receptor (EGFR), insulin-like growth factor-I receptor (IGF-IR) or c-kit (CD117) was identified in 77% of tumors. Loss of protein tyrosine phosphatase was found in 14%, whereas Akt activation was present in 28%. Several differences were identified between two subtypes of basal breast carcinomas: the pure variant (negative S-100 and actin) was more frequently associated with 'in situ carcinoma' (P ¼ 0.019) and pBad overexpression (P ¼ 0.098), whereas the myoepithelial variant (positive S-100 or actin) showed more frequent tumor necrosis (P ¼ 0.048), vimentin expression (P ¼ 0.0001), CD117 expression (P ¼ 0.001) and activated caspase-3 (P ¼ 0.089). IGF-IR could be as important as EGFR for the growth of these neoplasms. Basal cell carcinoma has at least two subtypes with distinct microscopic and immunohistochemical features.

Associations Between Mammography and Ultrasound Imaging Features and Molecular Characteristics of Triple-negative Breast Cancer

“…Posterior echo enhancement may also indicate an internal fluid element, such as in tumor necrosis, which is a feature regularly reported on pathological appraisal in TNBC (Lerma et al, 2007).…”

Increased insulin-like growth factor-1 receptor mRNA expression predicts poor survival in immunophenotypes of early breast carcinoma

“…Nevertheless, IGF1R may have some relevance in a subgroup of aggressive basal/triple-negative tumors. 2,37,38 It is noteworthy that in this study, phenotypes have been only stratified according to immunohistochemical and in situ hybridization (for HER2 tumors) results. In addition, besides the HR-positive status, Bcl2, p53 and Ki67 data were taken into consideration for classifying tumors into luminal A or luminal B, based on the important role of apoptosis and proliferation-related genes emphasized in previous studies, [39][40][41] and also supported by our study.…”

Combination therapy approaches to target insulin-like growth factor receptor signaling in breast cancer

“…IGF signaling has been shown to be a direct therapeutic target in TNBC (Creighton et al 2008, Bhargava et al 2011, Davison et al 2011. Briefly, IGF1R was shown to be expressed and activated by phosphorylation in TNBC (Lerma et al 2007, Law et al 2008, high IGF1R mRNA expression leads to poorer overall survival in basal/triple-negative groups (Peiro et al 2011) and rare high-level amplification of IGF1R has been detected in some basal-like breast cancers (Adelaide et al 2007). Collectively, these studies highlight that IGF1R is an oncogenic driver and therapeutic target in TNBC.…”