Abstract
Carcinomas with apocrine differentiation (CAD) of the breast are rare tumours typically presenting high immunohistochemical expression of androgen receptor (AR) which is a target molecule for personalised therapy. To date, no studies have evaluated the genetic changes that are associated with AR immunohistochemical expression in CADs. The present work aims to characterise AR status in CADs. Twenty CAD tumours were studied with immunohistochemistry, in situ fluorescence hybridization and DNA methylation analysis, to evaluate AR expression and its regulator status. All tumours demonstrated high AR immunohistochemical expression, with over 95% of the neoplastic cells showing AR positivity in 19/20 cases. CADs showed AR gene copy loss in a percentage of neoplastic cells ranging from 5 to 84% (mean 48.93%). AR regulator genes, including the MAGE family, UXT and FLNA, presented variable methylation levels, but were mainly hypomethylated and therefore all transcriptionally active. The results of this study indicate that CADs present AR monosomy, paralleled by higher transcriptional activity of the gene with potential to influence response to AR deprivation therapy.
Highlights
In the study of oestrogen (ER) and progesterone (PR) receptor-negative tumours, attention is currently focused on cases that express androgen receptor (AR)
In most of the cases, these tumours display the morphological features of carcinoma with apocrine differentiation (CAD) of the breast (1), composed of large cells with abundant, granular and eosinophilic cytoplasm, a centrally located nucleus with a thick nuclear membrane, coarse nuclear chromatin and a prominent nucleolus [1,2,3]
Cases were retained for the present study when they showed (a) ER and PR negativity and AR positivity; (b) the morphological and immunohistochemical profile consistent with the Fluorescent in situ hybridization (FISH) analysis was carried out using an Olympus BX61 epifluorescence microscope (Olympus, Melville, NY) equipped with a 100-planar objective
Summary
In the study of oestrogen (ER) and progesterone (PR) receptor-negative tumours, attention is currently focused on cases that express androgen receptor (AR). In most of the cases, these tumours display the morphological features of carcinoma with apocrine differentiation (CAD) of the breast (1), composed of large cells with abundant, granular and eosinophilic cytoplasm, a centrally located nucleus with a thick nuclear membrane, coarse nuclear chromatin and a prominent nucleolus [1,2,3]. CADs are generally triple negative or show HER2 amplification, in addition to strong and diffuse AR positivity on immunohistochemistry [1,2,3]. AR is a targetable molecule as has been demonstrated mainly in prostate [4] and, more recently, in male breast cancer [5]. Trials have been approved to evaluate anti-AR therapy efficacy in women affected by AR-positive tumours with promising results [4]
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