Is apocrine differentiation in breast carcinoma of prognostic significance?

Bundred, Nigel; Walker, R. A.; Everington, Dawn; White, G.K.; Stewart, Helen; Miller, W. R.

doi:10.1038/bjc.1990.240

Cited by 17 publications

(8 citation statements)

References 16 publications

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“…The importance of apocrine differentiation in breast carcinomas is uncertain because the incidence of apocrine change is difficult to establish, although extensive apocrine changes are reported in about 4% of invasive breast carcinomas. 41 Bundred et al 42 found that apocrine differentiation in breast carcinoma is associated with poor prognosis, although they could not explain the reasons for such, and suggested further investigation.…”

Section: Discussionmentioning

confidence: 97%

Loss of androgen receptor expression predicts early recurrence in triple-negative and basal-like breast cancer

et al. 2014

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Treatment of triple-negative invasive breast cancers, defined by the absence of estrogen and progesterone receptors and c-erbB2 expression, remains challenging. Androgen receptor, a member of the nuclear receptor superfamily that is involved in signaling pathways regulating cell proliferation, has been implicated in breast tumorigenesis. We immunohistochemically examined the expression of androgen receptor, basal markers (CK14, 34bE12) and EGFR in 699 triple-negative invasive breast cancers in tissue microarrays using the streptavidin-biotin method, and correlated the findings with clinical outcome. Positive androgen receptor expression was defined as staining of 1% or more of tumor cell nuclei. Survival outcomes were estimated with the Kaplan-Meier method and compared between groups with log-rank statistics. Cox proportional hazards models were used to determine the effect of androgen receptor on survival outcomes. Immunohistochemical positivity was observed in 38% of tumors, with the proportion of stained tumor cells ranging from 1 to 95% (mean 29%, median 10%). Androgen receptor expression was inversely associated with histologic grade and mitotic score. CK14, 34bE12 and EGFR confirmed 85% of cases to be basal-like, without significant association of basal-like phenotype with androgen receptor expression. Disease-free survival was significantly better in androgen receptor-positive triple-negative breast cancer, with a trend for improved overall survival. Decreased recurrence likelihood in both triple-negative and basal-like tumors (hazard ratio, 0.704; 95% confidence intervals, 0.498-0.994; P ¼ 0.0464; and hazard ratio, 0.675; 95% confidence intervals, 0.468-0.974; P ¼ 0.0355, respectively) was noted within 5 years of diagnosis but not thereafter. Our study suggests that loss of androgen receptor in triple-negative breast cancers augurs a worse prognosis, including those with basal-like features. More work in elucidating its relationship with mechanisms of progression, as well as trials of targeted treatment for androgen receptor-expressing triple-negative tumors, needs to be performed.

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Section: Discussionmentioning

confidence: 97%

Loss of androgen receptor expression predicts early recurrence in triple-negative and basal-like breast cancer

et al. 2014

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“…Many studies have confirmed that ZAG is a reliable immunohistochemical marker of apocrine cell differentiation of mammary epithelial tissues (7,8,35,36,(52)(53)(54)(55)(56). Sanchez et al (28) have shown that many proteins are expressed in breast cancer cell line, and ZAG is one of them.…”

Section: Zag As a Biomarkermentioning

confidence: 98%

Zinc α2-Glycoprotein: A Multidisciplinary Protein

Hassan

Waheed

Yadav

et al. 2008

Molecular Cancer Research

215

204

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Zinc A2-glycoprotein (ZAG) is a protein of interest because of its ability to play many important functions in the human body, including fertilization and lipid mobilization. After the discovery of this molecule, during the last 5 decades, various studies have been documented on its structure and functions, but still, it is considered as a protein with an unknown function. Its expression is regulated by glucocorticoids. Due to its high sequence homology with lipid-mobilizing factor and high expression in cancer cachexia, it is considered as a novel adipokine. On the other hand, structural organization and fold is similar to MHC class I antigen-presenting molecule; hence, ZAG may have a role in the expression of the immune response. The function of ZAG under physiologic and cancerous conditions remains mysterious but is considered as a tumor biomarker for various carcinomas. There are several unrelated functions that are attributed to ZAG, such as RNase activity, regulation of melanin production, hindering tumor proliferation, and transport of nephritic by-products. This article deals with the discussion of the major aspects of ZAG from its gene structure to function and metabolism. (Mol Cancer Res 2008;6(6):892 -906)

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“…Apocrine carcinoma is a rare lesion that represents about 0.5% of all invasive breast carcinomas according to the Danish Breast Cancer Cooperative Group (DBCG) Registry, and even though these lesions are morphologically distinct from other breast carcinomas, there are at present no available standard histopathological criteria for their diagnosis [2][3][4] and as a result, there is no precise information as to their prognosis. Molecular profiling of breast cancer tumours with cDNA microarrays have provided a new way to classify breast tumours in subgroups based on their expression patterns [5], as well as to derive signatures for prognosis [6][7][8] and response to treatment [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2006

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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.

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Is apocrine differentiation in breast carcinoma of prognostic significance?

Cited by 17 publications

References 16 publications

Loss of androgen receptor expression predicts early recurrence in triple-negative and basal-like breast cancer

Loss of androgen receptor expression predicts early recurrence in triple-negative and basal-like breast cancer

Zinc α2-Glycoprotein: A Multidisciplinary Protein

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

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