Abstract
Background:Basal-like breast carcinoma (BLBC) has attracted considerable attention over the past few years. It has been suggested that tumours expressing basal markers have a more aggressive clinical behaviour. However, a molecular basis for this disease remains unclear, and it lacks currently used therapeutic targets. Therefore developing a novel treatment strategy is crucial for improving the prognosis. The aim of this study was to characterise the immunohistochemical (IHC) expression of p16 in patients with BLBC compared with non-BLBC.Materials and methods:Eighty-five cases of grade-3 invasive ductal carcinomas not otherwise specified (IDC-NOS) were analyzed. Immunohistochemical stains for oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor type 2 (HER2), cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR) and p16 were performed. BLBC was defined as ER-, PR-, Her2- and CK5/6+, and/or EGFR+.Results:Twenty cases were categorised as BLBC versus 65 as non-basal. High mitotic count and presence of necrosis were associated with basal-like phenotype. Distant metastasis developed in 40% of cases of BLBC with frequent spread to brain and lung. p16 had significantly higher expression in the basal subgroup (80% versus 50.8%, P = 0.04). Patients with BLBCs were found to have a lower disease-free survival (DFS) rate (60% versus 70.8%, P = 0.03).Conclusion:BLBC typically demonstrates a unique profile. p16 is frequently expressed in breast cancers with basal-like phenotype; this suggests that p16 may play a role in the poor prognosis of this tumour, and it may be used in the development of a targeted therapy that will result in improved patient prognostication and outcome.
Highlights
Breast carcinomas are considered to be a heterogeneous group of tumours showing different behaviour, prognosis, and response to treatment [1]
Gene expression profiling analyses using DNA microarrays and later on immunohistochemical (IHC) studies have enabled the recognition of distinct subtypes of tumours associated with different clinical outcomes [3,4,5]: luminal A (positive for oestrogen receptor (ER) and progesterone receptor (PR) and negative for human epidermal growth factor receptor type 2 [HER2]); luminal B (ER+, PR+, HER2+); HER2 overexpressing (ER, PR, HER2+); basal-like; unclassifiable or normal breast-like
The aim of this study was to characterise the IHC expression of p16 in patients with Basal-like breast carcinoma (BLBC) compared with non-BLBC in a group of grade-3 invasive ductal carcinoma not otherwise specified (IDC-NOS) to identify a more homogenous subset to which targeted therapy can be applied
Summary
Breast carcinomas are considered to be a heterogeneous group of tumours showing different behaviour, prognosis, and response to treatment [1]. Nielsen et al [7] have developed an IHC panel for identifying BLBCs on the basis of a comparison between the transcriptomic and IHC profiles. According to this definition, BLBCs are negative for ER and HER2 and positive for CK5/6 and/or EGFR. P16 is frequently expressed in breast cancers with basal-like phenotype; this suggests that p16 may play a role in the poor prognosis of this tumour, and it may be used in the development of a targeted therapy that will result in improved patient prognostication and outcome Conclusion: BLBC typically demonstrates a unique profile. p16 is frequently expressed in breast cancers with basal-like phenotype; this suggests that p16 may play a role in the poor prognosis of this tumour, and it may be used in the development of a targeted therapy that will result in improved patient prognostication and outcome
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