The enigmatic nature of apocrine breast lesions

Abstract

Epithelial cells of fetal breast glandular structures, at the third trimester of pregnancy (28 weeks), produce GCDFP-15, in the absence of specific apocrine morphology. Apocrine epithelium of the breast may be a normal process of differentiation rather than a result of metaplasia, and it has been demonstrated that it is estrogen-receptor, progesterone-receptor and bcl-2 negative, but androgen-receptor (AR) positive. The significance of AR expression in apocrine epithelium is uncertain. Apocrine epithelium is seen in a wide spectrum of breast entities, ranging from benign lesions to invasive carcinoma. Breast cancer accounts 32% of all cancer cases among women and is the most common type of cancer in women. Little is known about breast carcinogenesis. Widely, it is accepted that breast cancer, like most other type of cancer, is being developed through the accumulation of genetic aberrations. Apocrine epithelium may reflect instability of the breast epithelium, creating an environment favouring further oncogenic alterations. In the last decade, several lines of evidence support the idea that some breast benign epithelial apocrine lesions are clonal lesions and may be considered as truly pre-malignant or precursors of breast carcinoma. Apocrine changes in many cases do not present any diagnostic difficulty; on the other hand, apocrine proliferations with cytologic atypia can be particularly difficult and challenging. The purpose of this study is to collect and highlight the areas of consensus in the literature as well as the controversial areas concerning the apocrine epithelium of the breast.

Lack of expression of androgen receptor may play a critical role in transformation from in situ to invasive basal subtype of high-grade ductal carcinoma of the breast

“…Pure apocrine carcinoma is uncommon and not included in the current study. Androgen receptor expression has been shown to be associated with apocrine carcinoma, which is often negative for ER and PR [33]. Leal et al [34] reported that the expression rates for AR, ER, PR, and HER-2 in 35 apocrine DCIS were 97.1%, 5.7%, 2.9%, and 47%, respectively, regardless of unclear grades.…”

Prolactin inducible protein in cancer, fertility and immunoregulation: structure, function and its clinical implications

“…Moreover, its role in human seminal fluid has been fully established [27 -31]. PIP is present at high concentration in BCF [32,33] and considered as a secretory marker of apocrine differentiation in breast carcinoma [34,35]. A large number of studies have been documented in the favor of aberrantly high expression of PIP in breast cancer specimens both at gene and protein levels [3, 36 -39].…”

Molecular and diagnostic features of apocrine breast lesions

“…Elayat et al [35] analyzed cell turnover in apocrine metaplasia and apocrine adenosis, concluding that apoptosis is not prevalent in such lesions and hypothesizing that at least some of them could be more susceptible to oncogenic changes. GCDFP-15, a 15-kD product of the AR target gene prolactin-induced protein, is often used as specific marker for apocrine differentiation and have been found in breast cysts [36] and breast cyst fluid [6,36].…”

“…However, apocrine metaplasia is observed in up to 85% of women without breast cancer and up to 95% of women with breast cancer, based on autopsy data [5]. Despite this high prevalence, the origin of apocrine differentiation in the breast remains controversial, and several theories have been proposed [6].…”