Biochemical study of cyst fluid in human breast cystic disease: a review

Enriori, Carlos L.; Novelli, Jorge; Cremona, Maria del Carmen; Hirsig, R. J. P.; Enriori, Pablo J.

doi:10.1007/bf01832352

Cited by 21 publications

(9 citation statements)

References 91 publications

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“…Cysts are divided into apocrine -or type I, flattened -or type II, and intermediate types based on the K + /Na + concentration ratio [31,[48][49][50][51]. Type I cysts (apocrine) have a higher K + /Na + ratio (P1.5) [48], and are lined by metaplastic apocrine secretory epithelium that exhibit tight cell-cell junctions.…”

Section: Apocrine Differentiation Of Breast Epithelial Cellsmentioning

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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Section: Apocrine Differentiation Of Breast Epithelial Cellsmentioning

confidence: 99%

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

et al. 2006

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“…Cysts are divided into apocrine (type I, acidophil cells), flattened (type II, basophil cells), and intermediate types based on the K ϩ /Na ϩ concentration ratio (5)(6)(7)(8)(9). Type I cysts have a higher K ϩ /Na ϩ ratio (Ն1.5) (5), are lined by metaplastic apocrine secretory epithelium that resembles sweat glands, and exhibit tight cell-cell junctions.…”

Section: And References Therein)mentioning

confidence: 99%

Apocrine Cysts of the Breast

Celis

Gromov

Moreira

et al. 2006

Molecular & Cellular Proteomics

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Up to one-third of women aged 30 -50 years have cysts in their breasts and are presumed to be at increased risk of developing breast cancer. Here we present an extensive proteomic and immunohistochemistry (IHC) study of breast apocrine cystic lesions aimed at generating specific biomarkers and elucidating the relationship, if existent, of apocrine cysts with cancer phenotype. To this end we compared the expression profiles of apocrine macrocysts obtained from mastectomies from high risk cancer patients with those of cancerous and non-malignant mammary tissue biopsies collected from the same patients. We identified two biomarkers, 15-hydroxyprostaglandin dehydrogenase and 3-hydroxymethylglutaryl-CoA reductase, that were expressed specifically by apocrine type I cysts as well as by apocrine metaplastic cells in type II microcysts, terminal ducts, and intraductal papillary lesions. No expression of these markers was observed in non-malignant terminal ductal lobular units, type II flat cysts, stroma cells, or fat tissue as judged by IHC analysis of matched non-malignant tissue samples collected from 93 high risk patients enrolled in our cancer program. IHC analysis of the corresponding 93 primary tumors indicated that most apocrine changes have little intrinsic malignant potential, although some may progress to invasive apocrine cancer. None of the apocrine lesions examined, however, seemed to be a precursor of invasive ductal carcinomas, which accounted for 81% of the tumors analyzed. Our studies also provided some insight into the origin, development, and enlargement of apocrine cysts in mammary tissue. The successful identification of differentially expressed proteins that characterize specific steps in the progression from early benign lesions to apocrine cancer opens a window of opportunity for designing and testing new approaches for pharmacological intervention, not only in a therapeutic setting but also for chemoprevention, to inhibit cyst development as both 15-hydroxyprostaglandin dehydrogenase and 3-hydroxymethylglutaryl-CoA reductase are currently being targeted for chemoprevention strategies in various malignancies. Molecular & Cellular Proteomics 5:462-483, 2006.The human breast presents many benign lesions that involve both the glandular and stromal tissues. These include fibrocystic changes, benign breast tumors, and breast inflammatory disease (1). Fibrocystic changes affect more than 50% of women during their lifetime and are comprised of cystic dilation of ducts, apocrine metaplasia of ductal epithelium, fibrosis, adenosis, and intraductal epithelial proliferation (Ref. and references therein).Cysts are fluid-filled sacs that usually develop in the upper half of the breast and are most common in women between 30 and 50 years of age (3). They are also found in menopausal women on hormone replacement therapy. Cysts start as a microscopic dilation of the ductules (microcyst) but can enlarge and reach sizes of a couple of centimeters in diameter (macrocysts) causing pain and discomfort due to the tens...

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“…In recent years, novel approaches to this issue have been offered by studies on the biochemical aspects of breast cyst fluid (BCF), and several reviews are available on protein, hormone, and electrolyte content [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Quantification of prostate-specific antigen immunoreactivity in human breast cyst fluids

Mannello

Bocchiotti²,

Bianchi

et al. 1996

Breast Cancer Res Tr

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The frequency of gross cystic breast disease in premenopausal women and its possible association with increased breast cancer risk emphasises the importance of investigations relating to breast cyst fluid composition. In order to contribute to a better analysis of this medium, we have measured the presence of prostate-specific antigen immuno-reactivity in sixty-four human breast cyst fluids. Data analyses show that 35% of samples presented a level of this antigen < 0.05 micrograms/L, whereas 42 out of 64 cysts show a significant increase in the mean value of metabolically active apocrine cysts when compared to flattened cysts (p < 0.01). We report the first evidence that breast epithelium of gross cysts produces, secretes, and accumulates large amounts of prostate-specific antigen, a glycoprotein produced by prostatic tissue but recently detected in breast tumours, normal tissues, and during pregnancy. The production and intracystic accumulation of this serine protease in biosynthetically active apocrine type cyst can play a feasible role in the natural history gross cystic breast disease as well as in the mechanism of cyst formation, enlargement, and transformation.

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Biochemical study of cyst fluid in human breast cystic disease: a review

Cited by 21 publications

References 91 publications

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

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

Apocrine Cysts of the Breast

Quantification of prostate-specific antigen immunoreactivity in human breast cyst fluids

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