Molecular and diagnostic features of apocrine breast lesions

Abstract

Apocrine morphology in breast is observed in a wide variety of lesions ranging from simple cysts and atypical hyperplasia to invasive metastatic stages of disease. The accurate diagnosis of breast apocrine carcinoma remains controversial, mainly due to the subjectivity of histopathological criteria and the lack of sensitive and specific biomarkers for reliable categorization of this subtype of breast carcinoma. Thus, many efforts are currently being made to identify novel molecular marker signature(s) that can define apocrine carcinoma with high levels of accuracy and reliability, and determine with certainty the true clinical significance of these lesions. The purpose of this article is to review the data on apocrine lesions, with an emphasis on borderline apocrine differentiation. In particular, we address relevant issues in the context of the current state of research on benign and malignant apocrine lesions of the breast, with a focus on parameters for diagnosis and potential-targeted therapeutic options.

All Benign and Malignant Apocrine Breast Lesions Over-Express Claudin 1 and 3 and Are Negative for Claudin 4

“…The finding of absent expression of claudin 4 in apocrine carcinoma, with its known good prognosis, is also consistent with the reported association between claudin 4 overexpression and poor prognosis and increased incidence of axillary and distant metastasis in breast carcinoma [8,9,19]. The finding is also consistent with the reported presence of an inverse relationship between claudin 4 and androgen receptor expression [19], as apocrine carcinomas are usually androgen receptor positive [22,24].…”

“…In this context, affecting other benign apocrine lesions that might be present in the breast at the same time, ought not to be of concern, particularly as some of these lesions; e.g. atypical apocrine adenosis, may have a pre-cancerous potential [22].…”

“…These included 117 excision, and 12 core biopsies. The diagnosis of benign and malignant apocrine lesions was based on the characteristic eosinophilic staining of the cytoplasm and was confirmed by immunostaining for Gross Cystic Disease Fluid Protein-15 (GCDFP-15) which showed strong diffuse expression of the protein in the majority of tumour cells [22]. All 45 morphologically non-apocrine tumours were also stained for GCDFP-15.…”

Atypical Apocrine Adenosis: Diagnostic Challenges and Pitfalls

“…GCDFP-15 is often used as a marker for carcinoma with apocrine features because it is related to androgen receptors; this association was proved by Naderi and Meyer. 26 A recent study 27 proposes and presents evidence suggesting that carcinomas with apocrine features arise from atypical and benign precursors. Gromol et al 27 compared several immunohistochemical markers in ductal carcinoma, carcinomas with apocrine features and apocrine DCIS.…”

“…26 A recent study 27 proposes and presents evidence suggesting that carcinomas with apocrine features arise from atypical and benign precursors. Gromol et al 27 compared several immunohistochemical markers in ductal carcinoma, carcinomas with apocrine features and apocrine DCIS. Their results show how malignant lesions acquire mutations as they become more aggressive.…”