Abstract:The levels of alpha 1-antitrypsin, transferrin, alkaline phosphatase, phosphohexoseisomerase and gamma-glutamyltransferase were measured in 32 samples of breast cyst fluid, and a wide range of values was obtained. The levels observed in some samples for these parameters, being similar to those of normal serum, might suggest a mechanism of plasma exudation for the formation of breast cyst fluid. Nevertheless, a comparison with the maximum normal serum reference value revealed very high levels of gamma-glutamylt… Show more
“…The electrophoretic map of BCF proteins revealed further fifteen polypeptides respect to those previously identified [103]; among these, a 1 -acid glycoprotein [104], a 1 -antichymotrypsin [111] and a 1 -antitrypsin [112], have been found at higher concentrations in apocrine Type I gross cysts respect to flattened Type II cysts. Their expression have been pathophysiologically linked to increased amounts of steroid hormones in GCBD [104].…”
Section: Miscellaneous Proteinsmentioning
confidence: 94%
“…Creatinine plays an important pathophysiological role in the cyst development [94]. The peculiar accumulation of ferritin and transferrin [112,122], plasminogen [135], b-thromboglobulin and thrombospondin [134,137] in Type I gross cysts has been suggested as clinical useful tool to distinguish the high biosynthetic activity of the apocrine 'metaplastic' cells, pathophysiologically linked to an active and selective accumulation process against a concentration gradient [137]. Among cell-adhesion molecules, only endothelin-1, ICAM-1, VCAM-1 and E-selectin have been reported occur in higher concentrations in apocrine Type I respect to flattened GCBD [119,130], suggesting a pathogenetic function mediated through paracrine/autocrine mechanisms [121], modulated in part by interleukins [130].…”
Section: Miscellaneous Proteinsmentioning
confidence: 99%
“…Some enzymes show activities that vary widely in BCF over a 300-fold range [23, 94,112,142,152,155,156], are pathophysiologically important influencing the ratio of unconjugated:glucuronidated estradiol [151], or hydrolysing fatty acid esters of steroids [147][148][149]. Increased Immunoglobulin M [103,127,128] Interleukin-1 (a e b) [129,130] Interleukin-2 [110,131] Interleukin-4 [132] Interleukin-6 [129,131] Interleukin-8 [131] Intercellular adhesion molecule-1 (ICAM-1) [129] a-Lactalbumin [123,133] Lactoferrin [21, 106,107] Lysozyme [103,107] Oncostatin M [131] Platelet factor-4 [134] Plasminogen [135] pS 2 [136] Steroid-binding globulin [82,105] b-Thromboglobulin [134] Thrombospondin [134,137] Tissue-type plasminogen activator [135] Transcortin-like protein [138] Transferrin [103,112,122] Urokinase-like plasminogen activator [135] Vascular cell adhesion molecule-1 (VCAM-1) [121] Zn-a 2 -glycoprotein (GCDFP-44) [103,10...…”
For more than one and a half century the cystic disease of the breast has been recognized as the most frequent female benign breast lesion. Although some conundrums and controversies exist about the relation between gross cysts and breast cancer, recent evidence suggests that the multidisciplinary study of gross cystic breast disease (GCBD) may be a powerful tool for predicting the natural history of the multifaceted gross cyst pathology. A lot of papers have been published on breast cyst fluids (BCF) concerning biochemical, hormonal and morphological aspects, demonstrating that the intracystic fluid contains a wide variety of components (such as ions, lipids, proteins, enzymes, growth factors and antigens) and suggesting that their profile provides additional knowledge on both physiopathology and etiologic pathways of human gross cystic breast disease. The aim of this overview is the critical evaluation of all data accumulated in the last thirty years, in order to highlight the utility of biochemical and epidemiological studies to identify gross cysts, if any, at higher breast cancer risk.
“…The electrophoretic map of BCF proteins revealed further fifteen polypeptides respect to those previously identified [103]; among these, a 1 -acid glycoprotein [104], a 1 -antichymotrypsin [111] and a 1 -antitrypsin [112], have been found at higher concentrations in apocrine Type I gross cysts respect to flattened Type II cysts. Their expression have been pathophysiologically linked to increased amounts of steroid hormones in GCBD [104].…”
Section: Miscellaneous Proteinsmentioning
confidence: 94%
“…Creatinine plays an important pathophysiological role in the cyst development [94]. The peculiar accumulation of ferritin and transferrin [112,122], plasminogen [135], b-thromboglobulin and thrombospondin [134,137] in Type I gross cysts has been suggested as clinical useful tool to distinguish the high biosynthetic activity of the apocrine 'metaplastic' cells, pathophysiologically linked to an active and selective accumulation process against a concentration gradient [137]. Among cell-adhesion molecules, only endothelin-1, ICAM-1, VCAM-1 and E-selectin have been reported occur in higher concentrations in apocrine Type I respect to flattened GCBD [119,130], suggesting a pathogenetic function mediated through paracrine/autocrine mechanisms [121], modulated in part by interleukins [130].…”
Section: Miscellaneous Proteinsmentioning
confidence: 99%
“…Some enzymes show activities that vary widely in BCF over a 300-fold range [23, 94,112,142,152,155,156], are pathophysiologically important influencing the ratio of unconjugated:glucuronidated estradiol [151], or hydrolysing fatty acid esters of steroids [147][148][149]. Increased Immunoglobulin M [103,127,128] Interleukin-1 (a e b) [129,130] Interleukin-2 [110,131] Interleukin-4 [132] Interleukin-6 [129,131] Interleukin-8 [131] Intercellular adhesion molecule-1 (ICAM-1) [129] a-Lactalbumin [123,133] Lactoferrin [21, 106,107] Lysozyme [103,107] Oncostatin M [131] Platelet factor-4 [134] Plasminogen [135] pS 2 [136] Steroid-binding globulin [82,105] b-Thromboglobulin [134] Thrombospondin [134,137] Tissue-type plasminogen activator [135] Transcortin-like protein [138] Transferrin [103,112,122] Urokinase-like plasminogen activator [135] Vascular cell adhesion molecule-1 (VCAM-1) [121] Zn-a 2 -glycoprotein (GCDFP-44) [103,10...…”
For more than one and a half century the cystic disease of the breast has been recognized as the most frequent female benign breast lesion. Although some conundrums and controversies exist about the relation between gross cysts and breast cancer, recent evidence suggests that the multidisciplinary study of gross cystic breast disease (GCBD) may be a powerful tool for predicting the natural history of the multifaceted gross cyst pathology. A lot of papers have been published on breast cyst fluids (BCF) concerning biochemical, hormonal and morphological aspects, demonstrating that the intracystic fluid contains a wide variety of components (such as ions, lipids, proteins, enzymes, growth factors and antigens) and suggesting that their profile provides additional knowledge on both physiopathology and etiologic pathways of human gross cystic breast disease. The aim of this overview is the critical evaluation of all data accumulated in the last thirty years, in order to highlight the utility of biochemical and epidemiological studies to identify gross cysts, if any, at higher breast cancer risk.
“…The biochemical composition of BCF has been studied in order to understand the controlling mechanism of cyst formation as well as to define its possible role in carcinogenesis. Data are also available for its ionic composition [4,7], enzyme levels [8,9], hormone content [10], protein components [11][12][13][14], and cytological features [15].…”
Benign mammary gross cystic disease is the most common breast lesion. Women with apocrine changes of epithelium lining the cysts are at higher risk for developing breast cancer than the normal female population. Sialic acid has drawn considerable interest because of carbohydrate aberrations in malignant cells. The current investigation determined the concentrations of lipid-associated sialic acid (LASA) in 62 breast cyst fluids and sera. Data analyses show a significant increase in the mean values of LASA in metabolically active apocrine cysts when compared to the cysts with Na+/K+ > 3 (flattened cysts) (p < 0.001). The greater LASA levels in cyst fluids with lower intracystic Na+/K+ ratios could represent an altered expression of biosynthetic activity of the surrounding apocrine cell surface sialoglycolipid metabolism, providing a possible explanation of why women with apocrine cysts may be at greater cancer risk and being useful in further studies on functional stage changes in the cysts and their relationship to breast cancer.
Gross cystic breast disease (GCBD) is the most common benign breast disorder, but the molecular basis of cyst formation remains to be identified. If the use of aluminium-based antiperspirant salts is involved in the etiology of gross breast cyst formation, it might be expected that aluminium would be at elevated levels in human breast cyst fluid (BCF). Aluminium was measured by ICP-MS in 48 samples of BCF, 30 samples of human blood serum and 45 samples of human breast milk at different stages of lactation (colostrum, intermediate, mature). The median level of aluminium in apocrine type I BCF (n = 27, 150 microg l(-1)) was significantly higher than in transudative type II BCF (n = 21, 32 microg l(-1); P < 0.0001). By comparison, aluminium measurements gave a median concentration of 6 microg l(-1) in human serum and 25 microg l(-1) in human breast milk, with no difference between colostrum, intermediate and mature milk. Levels of aluminium were significantly higher in both types of BCF than in human serum (P < 0.0001). However when compared with human breast milk, aluminium levels were only significantly higher in apocrine type I BCF (P < 0.0001) and not in transudative type II BCF (P = 0.152). It remains to be identified why such high levels of aluminium were found in the apocrine type I BCF and from where the aluminium originated. However, if aluminium-based antiperspirants are found to be the source and to play any causal role in development of breast cysts, then it might become possible to prevent this common breast disorder.
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