Molecular pathology of breast apocrine carcinomas: A protein expression signature specific for benign apocrine metaplasia

Abstract

Breast cancer is a heterogeneous disease that encompasses a wide range of histopathological types including: invasive ductal carcinoma, lobular carcinoma, medullary carcinoma, mucinous carcinoma, tubular carcinoma, and apocrine carcinoma among others. Pure apocrine carcinomas represent about 0.5% of all invasive breast cancers according to the Danish Breast Cancer Cooperative Group Registry, and despite the fact that they are morphologically distinct from other breast lesions, there are at present no standard molecular criteria available for their diagnosis. In addition, the relationship between benign apocrine changes and breast carcinoma is unclear and has been a matter of discussion for many years. Recent proteome expression profiling studies of breast apocrine macrocysts, normal breast tissue, and breast tumours have identified specific apocrine biomarkers [15-hydroxyprostaglandin dehydrogenase (15-PGDH) and hydroxymethylglutaryl coenzyme A reductase (HMG-CoA reductase)] present in early and advanced apocrine lesions. These biomarkers in combination with proteins found to be characteristically upregulated in pure apocrine carcinomas (psoriasin, S100A9, and p53) provide a protein expression signature distinctive for benign apocrine metaplasias and apocrine cystic lesions. These studies have also presented compelling evidence for a direct link, through the expression of the prostaglandin degrading enzyme 15-PGDH, between early apocrine lesions and pure apocrine carcinomas. Moreover, specific antibodies against the components of the expression signature have identified precursor lesions in the linear histological progression to apocrine carcinoma. Finally, the identification of proteins that characterize the early stages of mammary apocrine differentiation such as 15-PGDH, HMG-CoA reductase, and cyclooxygenase 2 (COX-2) has opened a window of opportunity for pharmacological intervention, not only in a therapeutic manner but also in a chemopreventive setting. Here we review published and recent results in the context of the current state of research on breast apocrine cancer.

15-Prostaglandin Dehydrogenase Expression Alone or in Combination with ACSM1 Defines a Subgroup of the Apocrine Molecular Subtype of Breast Carcinoma

“…IACs are generally considered as a variant of IDC (8,10,15), although Japaze et al (11) recently defined separate histopathological criteria for the diagnosis of pure IACs, which have a less aggressive behavior than IDC-NST. The identification of apocrine carcinomas is further complicated by the fact that some of the less differentiated carcinomas may actually represent apocrine carcinomas that have lost their apocrine morphological characteristics, making it difficult to distinguish them from IDC-NST using purely morphological criteria (16,17). As a result, it is likely that IACs are more frequent than previously estimated.…”

“…Moreover some are positive for the gross cystic disease fluid protein-15 (GCDFP-15) (9, 24 -26), a marker that it is, however, not specific for these lesions (16,17,25). p53 expression has been observed in about 50% of invasive apocrine carcinomas (19,27), and there have been some reports addressing the characteristics of apocrine lesions using loss of heterozygosity (22,28,29) and comparative genome hybridization (10,30).…”

EGFR and HER-2/neu expression in invasive apocrine carcinoma of the breast

“…17 Although apocrine carcinoma exhibits distinctive histopatological and molecular features, the lack of standardized diagnostic criteria has produced controversial and heterogeneous results in the scientific literature in terms of its immunohistochemical profile and molecular classification. 2,[18][19][20] The erbB (HER) family is comprised of four homologous transmembrane receptors involved in growth factor cellular signaling. 21 Epidermal growth factor receptor (EGFR) (or HER-1) and HER-2/neu genes are of particular importance in breast cancer pathogenesis as their activation and coexpression are associated with an aggressive clinical course and a poor outcome.…”

“…[1][2][3] Apocrine differentiation is defined by the presence of large cells with prominent eosinophilic, flocculent cytoplasm, with sharply defined cell borders, and with large nuclei containing prominent macronucleoli. Importantly, a characteristic steroid receptor expression profile further defines these tumors as consistently estrogen receptor (ER) negative, progesterone receptor (PR) negative and androgen receptor (AR) positive.…”

Low doses x-ray irradiation influence on liver detoxication system in rats with transplanted guerin's carcinoma

“…Известно [16], что развитие в организме злокачественного образования сопровождается усиленным продуцированием токсических для организма веществ, основная часть которых обезвреживается клетками печени. Поэтому исследование активностей компонентов детоксикационной системы печени крыс на разных стадиях развития опухоли в организме может служить критерием генотоксического действия продуктов метаболизма опухолевой ткани на отдалённые органы.…”