Breast Cancer Research and Treatment

, Volume 97, Issue 2, pp 115–129 | Cite as

Human gross cyst breast disease and cystic fluid: bio-molecular, morphological, and clinical studies

  • Ferdinando Mannello
  • Gaetana Anna Maria Tonti
  • Stefano Papa
Review

Summary

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.

Keywords

breast cancer risk biochemistry clinical evaluation cyst type cytology epidemiology gross cystic breast disease molecular biology 

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References

  1. 1.
    Cooper AP, 1845. The anatomy and diseases of the breast. Lea and Blanchard, PhiladelphiaGoogle Scholar
  2. 2.
    Reclus P, 1883 La maladie kystique des mamelles Bull Soc Anat Paris 58: 428–433Google Scholar
  3. 3.
    Schimmelbusch C, 1892 Das cystadenoma der mamma Arch Klin Chir 44: 117–134Google Scholar
  4. 4.
    Ahmed A, 1978. Atlas of the ultrastructure of human breast diseases. Churchill Livingstone, New York Google Scholar
  5. 5.
    Bodian CA, 1993 Benign breast diseases, carcinoma in situ, and breast cancer risk Epidem Rev 15: 177–187Google Scholar
  6. 6.
    Mannello F, Malatesta M, Gazzanelli G, 1999 Breast cancer in women with palpable breast cysts Lancet 354: 677–678PubMedGoogle Scholar
  7. 7.
    Frantz VK, Pickren JW, Melcher GW, Auchincloss H Jr., 1951 Incidence of chronic cystic disease in so-called normal breasts: study based on 225 post-mortem examinations Cancer 4: 762–783PubMedGoogle Scholar
  8. 8.
    Haagensen CD, 1986. Diseases of the breast. WB Saunders Co., Philadelphia Google Scholar
  9. 9.
    Brenner RJ, Bein ME, Sarti DA, Vinstein AL, 1994 Spontaneous regression of interval benign cysts of the breast Radiology 193: 365–368PubMedGoogle Scholar
  10. 10.
    Norlock FE, 2002 Benign breast pain in women: a practical approach to evaluation and treatment JAMWA 57: 85–90PubMedGoogle Scholar
  11. 11.
    Santen RJ, Mansel R, 2005 Benign breast disorders N Engl J Med 353: 275–285PubMedGoogle Scholar
  12. 12.
    Semb C, 1928 Pathological-anatomical and clinical investigations of fibro-adenomatosis cystica mammae and its relation to other pathological conditions in mamma, especially cancer Acta Chir Scandinav 64(Suppl. 10): 1–484Google Scholar
  13. 13.
    Dixon JM, Mansel RE, 1995 Pigments in breast fluids: What are they? BMJ 310: 402–403Google Scholar
  14. 14.
    Malatesta M, Mannello F, Sebastiani M, Cardinali A, Marcheggiani F, Renò F, Gazzanelli G, 1998 Ultrastructural characterization and biochemical profile of human gross cystic breast disease Breast Cancer Res Treat 48: 211–219PubMedGoogle Scholar
  15. 15.
    Love SM, Gelman RS, Silen W, 1982 Fibrocystic disease of the breast: a nondisease? N Engl J Med 307: 1010–1014PubMedGoogle Scholar
  16. 16.
    Minton JP, Abou-Issa H, Reiches N, Roseman JM, 1981 Clinical and biochemical studies on methylxanthine-related fibrocystic breast disease Surgery 90: 299–304PubMedGoogle Scholar
  17. 17.
    Horner NK, Lampe JW, 2000 Potential mechanisms of diet therapy for fibrocystic breast conditions show inadequate evidence of effectiveness J Am Diet Assoc 100: 1368–1380PubMedGoogle Scholar
  18. 18.
    Webb PM, Byrne C, Schnitt SJ, Connolly JL, Jacobs TW, Baer HJ, Willett WC, Colditz GA, 2004 A prospective study of diet and benign breast disease Cancer Epidemiol Biomarkers Prev 13: 1106–1113PubMedGoogle Scholar
  19. 19.
    Michels KB, Holmberg L, Bergkvist L, Wolk A, 2002 Coffee, tea, and caffeine consumption and breast cancer incidence in a cohort of Swedish women Ann Epidemiol 12: 21–26PubMedGoogle Scholar
  20. 20.
    Dogliotti L, Orlandi F, Caraci P, Puligheddu B, Torta M, Angeli A, 1990 Biochemistry of breast cyst fluid: an approach to understanding intercellular communication in the terminal duct lobular units Ann NY Acad Sci USA 586: 17–28Google Scholar
  21. 21.
    Molina R, Filella X, Herranz M, Prats M, Velasco A, Zanon G, Martinez-Osaba MJ, Ballesta AM, 1990 Biochemistry of cyst fluid in fibrocystic disease of the breast: approach to classification and understanding of the mechanism of formation Ann NY Acad Sci USA 586: 29–42Google Scholar
  22. 22.
    Angeli A, Dogliotti L, Orland F, Beccati D, 1987 Mammary cysts: pathophysiology and biochemistry Nucl Med Biol 14: 397–406Google Scholar
  23. 23.
    Sartorius OW, 1995 The biochemistry of breast cyst fluids and duct secretions Breast Cancer Res Treat 35: 255–266PubMedGoogle Scholar
  24. 24.
    Dixon JM, Scott WN, Miller WR, 1985 Natural history of cystic disease: importance of cyst type Br J Surg 72: 190–192PubMedGoogle Scholar
  25. 25.
    Beccati D, Grilli N, Schincaglia P, Naldoni C, Tavolazzi L, Ranaldi R, Dogliotti L, Torta M, Angeli A, 1988 Apocrine cells in breast cyst fluid and their relationship to cyst type: a morphometric study Eur J Cancer Clin Oncol 24: 597–602PubMedGoogle Scholar
  26. 26.
    Naldoni C, Bruzzi P, Bucchi S, Gordini M, Torta M, Caraci P, Orlandi F, 1990 Cohort study of women affected by gross cystic disease: correlation between cationic and hormonal composition of breast cyst fluid and the risk of breast cancer Ann NY Acad Sci USA 586: 272–275Google Scholar
  27. 27.
    Vizoso F, Fueyo A, Allende MT, Fernandez J, Garcia-Moran M, Ruibal A, 1990 Evaluation of human breast cysts according to their biochemical and hormonal composition, and cytological examination Eur J Surg Oncol 16: 209–214PubMedGoogle Scholar
  28. 28.
    Dixon JM, Miller WR, Scott WN, 1983 The morphological basis of human breast cyst populations Br J Surg 70: 604–606PubMedGoogle Scholar
  29. 29.
    Ebbs SR, Bates T, 1988 Breast cyst type does not predict the natural history of cystic disease or breast cancer Br J Surg 75: 702–704PubMedGoogle Scholar
  30. 30.
    Angeli A, Bradlow HL, Bodian CA, Chasalow FI, Dogliotti L, Haagensen DE Jr., 1990 Criteria for classifying breast cyst fluids Ann NY Acad Sci USA 586: 49–53Google Scholar
  31. 31.
    Hartmann LC, Sellers TA, Frost MH, Lingle WL, Degnim AC, Vierkant RA, Maloney SD, Pankratz VS, Hillman DW, Suman VJ, Johnson J, Blake C, Tlsty T, Vachon CM, Melton III LJ, Visscher DW, 2005 Benign breast disease and the risk of breast cancer N Engl J Med 353: 229–237PubMedGoogle Scholar
  32. 32.
    Krieger N, Hiatt RA, 1992 Risk of breast cancer after benign breast disease Am J Epidemiol 135: 619–631PubMedGoogle Scholar
  33. 33.
    Ciatto S, Biggeri A, Rosselli Del Turco M, Bartoli D, Iossa A, 1990 Risk of breast cancer subsequent to proven gross cystic disease Eur J Cancer 26: 555–557PubMedGoogle Scholar
  34. 34.
    Naldoni C, Costantini M, Dogliotti L, Bruzzi P, Bucchi L, Buzzi G, Torta M, Angeli A, 1992 Association of cyst type with risk factors for breast cancer and relapse rate in women with gross cystic disease of the breast Cancer Res 52: 1791–1795PubMedGoogle Scholar
  35. 35.
    Hodge J, Surver J, Aponte GG, 1959 Relationship of fibrocystic disease to carcinoma of breast; study based on 876 cases AMA Arch Surg 79: 670–678PubMedGoogle Scholar
  36. 36.
    Page DL, Van der Zwaag R, Rogers LW, Williams LT, Walker WE, Hartmann WH, 1978 Relation between component parts of fibrocystic disease complex and breast cancer J Natl Cancer Inst 61: 1055–1063PubMedGoogle Scholar
  37. 37.
    Harrington LE, Lesnick G, 1981 The association between gross cysts of the breast and breast cancer Breast 7: 113–117Google Scholar
  38. 38.
    Campbell OJ, 1934 Relationship between cystic disease of breast and carcinoma Arch Surg 28: 1001–1056Google Scholar
  39. 39.
    Foote FW, Stewart FW, 1945 Comparative studies of cancerous versus noncancerous breasts Ann Surg 121: 6–53PubMedGoogle Scholar
  40. 40.
    Potter JF, Slimbaugh WP, Woodward SC, 1968 Can breast be anticipated?: a follow-up of benign breast biopsies Ann Surg 167: 829–838PubMedGoogle Scholar
  41. 41.
    Gallager HS, Martin JE, 1969 Early phases in the development of breast cancer Cancer 24: 1170–1178PubMedGoogle Scholar
  42. 42.
    Black MM, Barclay THC, Cutler SJ, Hankey BF, Asire AJ, 1972 Association of atypical characteristics of benign breast lesions with subsequent risk of breast cancer Cancer 29: 338–343PubMedGoogle Scholar
  43. 43.
    Jensen HM, Rice JR, Wellings SR, 1976 Preneoplastic lesions in the human breast Science 191: 295–297PubMedGoogle Scholar
  44. 44.
    Dupont WD, Page DL, 1985 Risk factors for breast cancer in women with proliferative breast disease N Engl J Med 312: 146–151PubMedGoogle Scholar
  45. 45.
    Page DL, Dupont WD, 1985 Are breast cysts a premalignant marker? Eur J Clin Oncol 21:635–636Google Scholar
  46. 46.
    Cancer Committee of the College of American Pathologists: Is “fibrocystic disease” of the breast precancerous? Arch Pathol Lab Med 110: 171–173, 1986Google Scholar
  47. 47.
    Warren S, 1940. Relation of “chronic mastitis” to carcinoma of breast Surg Gynec Obst 71: 257–273 Google Scholar
  48. 48.
    Clagett OT, Plimpton NC, Root GT, 1944 Lesions of breast: relationship of benign lesions to carcinoma Surgery 15: 413–419Google Scholar
  49. 49.
    Davis HH, Simons M, Davis JB, 1964 Cystic disease of the breast: relationship to carcinoma Cancer 17: 957–978PubMedGoogle Scholar
  50. 50.
    Veronesi U, Pizzocaro G. 1968 Breast cancer in women subsequent to cystic disease of the breast Surg Gynecol Obstet 126: 529–532PubMedGoogle Scholar
  51. 51.
    Chardot C, Varroyi A, Parach RM, 1970 Mastose fibro-kystique et cancer Bull Cancer 57: 251–268PubMedGoogle Scholar
  52. 52.
    Donnelly PK, Baker KW, Carney JA, O’Fallon WM, 1975 Benign breast lesions and subsequent breast carcinoma in Rochester, Minnesota Mayo Clin Proc 50: 650–656PubMedGoogle Scholar
  53. 53.
    Kodlin D, Winger EE, Morgenstern NL, Chen U, 1977 Chronic mastopathy and breast cancer: a follow-up study Cancer 39: 2603–2607PubMedGoogle Scholar
  54. 54.
    Hutchinson WB, Thomas DB, Hamlin WB, Roth GJ, Peterson AV, Williams B, 1980 Risk of breast cancer in women with benign breast disease J Natl Cancer Inst 65:13–20PubMedGoogle Scholar
  55. 55.
    Jones BM, Bradbeer JW, 1980 The presentation and progress of macroscopic breast cysts Br J Surg 67: 69–71Google Scholar
  56. 56.
    Roberts MM, Jones V, Elton RA, 1984 Risk of breast cancer in women with a history of benign disease of the breast BMJ 288: 275–278PubMedGoogle Scholar
  57. 57.
    Brinton LA, 1990 Relationship of benign breast disease to breast cancer Ann NY Acad Sci 586: 266–271PubMedGoogle Scholar
  58. 58.
    Bundred NJ, West RR, O’Dowd J, Mansel RE, 1991 Is there an increased risk of breast cancer in women who have had a breast cyst aspirated? Br J Cancer 64: 953–955PubMedGoogle Scholar
  59. 59.
    Bruzzi P, Bucchi L, Costantini M, Naldoni C, 1990 Follow-up studies of patients with categorized breast cysts: methodological issues Ann NY Acad Sci 586: 43–48PubMedGoogle Scholar
  60. 60.
    Dixon JM, McDonald C, Elton RA, Miller WR, 1999 Risk of breast cancer in women with palpable breast cysts: a prospective study Lancet 353: 1742–1745PubMedGoogle Scholar
  61. 61.
    Budai B, Számel I, Sulyok Z, Német M, Bak M, Ottò SZ, Reed MJ, Purohit A, Parish DC, Kralovanszky J, 2001 Characteristics of cystic breast disease with special regard to breast cancer development Anticancer Res 21: 749–752PubMedGoogle Scholar
  62. 62.
    Enriori CL, Novelli JE, Cremona MC, Hirsig RJP, Enriori PJ, 1992 Biochemical study of cyst fluid in human breast cystic disease: a review Breast Cancer Res Treat 24: 1–8PubMedGoogle Scholar
  63. 63.
    Dixon JM, Lumsden AB, Miller WR, 1985 The relationship of cyst type to risk factors for breast cancer and the subsequent development of breast cancer in patients with breast cystic disease Eur J Cancer Clin Oncol 21: 1047–1050PubMedGoogle Scholar
  64. 64.
    Hutter RVP, 1985 Good-bye to fibrocystic disease N Engl J Med 312:179–181PubMedGoogle Scholar
  65. 65.
    Baum M, 1999 Breast cancer in women with palpable breast cysts Lancet 354: 677PubMedGoogle Scholar
  66. 66.
    Papanicolaou GN, Holmquist DG, Bader BM, Falk EA, 1958 Exfoliative cytology of human mammary gland and its value in diagnosis of cancer and other diseases of breast Cancer 11: 377–409PubMedGoogle Scholar
  67. 67.
    Dabbs D, 1993 Mammary ductal foam cells: macrophage immunophenotype Human Pathol 24:977–981Google Scholar
  68. 68.
    Zanardi S, Valenti G, Torrisi R, Maisto L, Nicolò G, Barreca A, Minuto F, Boccardo F, 1991 Identification of breast cyst subpopulations: biochemical and morphological features Cancer Detect Prev 15: 273–276PubMedGoogle Scholar
  69. 69.
    Tsung JSH, Wang TY, Wang SM, Yang PS, 2005 Cytological and biochemical studies of breast cyst fluid. Breast 14: 37–41PubMedGoogle Scholar
  70. 70.
    Cowen PN, Benson EA, 1979 Cytological study of fluid from breast cysts Br J Surg 66: 209–211PubMedGoogle Scholar
  71. 71.
    Ciatto S, Cariaggi P, Bulgaresi P, 1987 The value of routine cytologic examination of breast cyst fluids Acta Cytol 31: 301–304PubMedGoogle Scholar
  72. 72.
    Hindle WH, Arias RD, Florentine B, Whang J, 2000 Lack of utility in clinical practice of cytologic examination of nonbloody cyst fluid from palpable breast cysts Am J Obstet Gynecol 182: 1300–1305PubMedGoogle Scholar
  73. 73.
    Tabar L, Pentek Z, Dean PB, 1981 The diagnostic and therapeutic value of breast cyst puncture and pneumocystography Radiology 141: 659–663PubMedGoogle Scholar
  74. 74.
    Stella F, Biagioni S, Stella C, Cerroni L, Troccoli R, 1984 La citologia delle cisti mammarie Quad Sclavo Diagn 20: 283–294PubMedGoogle Scholar
  75. 75.
    Toth J, Szamel I, Svastic E, DeSombre ER, 1990 Significance of apocrine metaplasia in mammary carcinogenesis Ann NY Acad Sci 586: 238–251PubMedGoogle Scholar
  76. 76.
    Athanassiadou PP, Veneti SZ, Kyrkou KA, Intzes KS, Mouzaka LI, Papadimitriou GK, 1992 Presence of epidermal growth factor receptor in breast smears of cyst fluids: relationship to electrolyte ratios and pH concentration Cancer Detect Prev 16: 113–118PubMedGoogle Scholar
  77. 77.
    Murad TM, von Haam E, 1968 The ultrastructure of fibrocystic disease of the breast Cancer 22: 587–600PubMedGoogle Scholar
  78. 78.
    Nagy GK, Jacobs JB, Mason-Savas A, Pomerantz SN, DeCiero GJ, 1989 Intracytoplasmic eosinophilic inclusion bodies in breast cyst fluids are giant lysosomes Acta Cytol 33: 99–103PubMedGoogle Scholar
  79. 79.
    Simpson JF, Page DL, 1993 Loss of expression of fodrin (a structural protein) in cystic changes of human breast Lab Invest 68: 537–540PubMedGoogle Scholar
  80. 80.
    Pullinger BD, 1947 Cystic disease of the breast: human and experimental Lancet 2: 567–572PubMedGoogle Scholar
  81. 81.
    Angeli A, Bradlow HL, Dogliotti L, 1986 Endocrinology of the breast: basic and clinical aspects: Part III-VI Ann NY Acad Sci 464: 100–400Google Scholar
  82. 82.
    Rosner W, Khan MS, Breed CN, Fleisher M, Bradlow HL, 1985 Plasma steroid-binding proteins in the cysts of gross cystic disease of the breast J Clin Endocrinol Metab 61: 200–203PubMedGoogle Scholar
  83. 83.
    Angeli A, Dogliotti L, Naldoni C, Orlandi F, Puligheddu B, Caraci P, Bucchi L, Torta M, Bruzzi P, 1994 Steroid biochemistry and categorization of breast cyst fluid: relation to breast cancer risk J Steroid Biochem Molec Biol 49: 333–339PubMedGoogle Scholar
  84. 84.
    Conway W, Flanagan P, Naughton P, Sharp M, Murray M, O’Higgins N, 1987 The clinical, biochemical and hormonal features of breast cysts Irish Med J 80: 164–166Google Scholar
  85. 85.
    Budai B, Szamel I, Sulyok Z, Nemeth M, Bak M, Kralovanszky J, Otto SZ, Besznyak I, Purohit A, Parish DC, Reed MJ, 2000 Influence of hormonal status of patients with cystic disease on the composition of cyst fluid and breast cancer risk Anticancer Res 20: 3879–3886PubMedGoogle Scholar
  86. 86.
    Fleisher M, Robbins G, Poseed C, Fracchia A, Urban J, Schwartz M, 1973 Biochemistry of breast cyst fluid Meml Sloan Kettering Clin Bull 3: 95Google Scholar
  87. 87.
    Fleisher M, Bradlow HL, Schwartz MK, Schwartz D, Breed C, 1984 The anion gap in human breast cyst fluid: a possible high risk indicator for breast cancer Clin Chem 30: 940Google Scholar
  88. 88.
    Bradlow HL, Skidmore FD, Schwartz MK, Fleisher M, 1981 Cation levels in human breast cyst fluid Clin Oncol 7: 388–390PubMedGoogle Scholar
  89. 89.
    Miller WR, Dixon JM, Scott WN, Forrest APM, 1983 Classification of human breast cysts according to electrolyte and androgen conjugate composition Clin Oncol 9: 227–232PubMedGoogle Scholar
  90. 90.
    Dogliotti R, Orlandi F, Torta M, Buzzi G, Naldoni C, Mazzotti A, Angeli A, 1986 Cations and dehydroepiandrosterone-sulfate in cyst fluid of pre- and menopausal patients with gross cystic disease of the breast: evidence for the existence of subpopulations of cysts Eur J Cancer Clin Oncol 22: 1301–1307PubMedGoogle Scholar
  91. 91.
    Boccardo F, Valenti G, Zanardi S, Cerruti G, Fassio T, Bruzzi P, De Franchis V, Barreca A, Del Monte P, Minuto F, 1988 Epidermal growth factor in breast cyst fluid: relationship with intracystic cation and androgen conjugate content Cancer Res 48: 5860–5863PubMedGoogle Scholar
  92. 92.
    Suarez B, Vizoso F, Fueyo A, Allende MT, Fernandez Fernandez M, Fdez LLana B, Roiz MC, Ruibal A, 1992 Active androgens in breast cyst fluids Int J Biol Markers 7: 263–264PubMedGoogle Scholar
  93. 93.
    Sanchez LM, Vizoso F, Allende MT, Ruibal A, Lopez-Otin C, 1992 Quantification and molecular analysis of cathepsin D in breast cyst fluids Eur J Cancer 28: 828–832Google Scholar
  94. 94.
    Simickova M, Pecen L, Eben K, Nekulova M, Vermousek I, Stratil P, Rejthar A, Cernoch M, Lang B, Sakalova J, 1994 Biochemical analysis of breast cyst fluid as a possible predictor of breast carcinoma development Neoplasma 41: 245–252Google Scholar
  95. 95.
    Martinez L, Castilla JA, Gil T, Molina J, Diaz MA, Mozas J, Herruzo A, 1995 Intracystic lipidic profile in fibrocystic breast disease Gynecol Endocrinol 8: 287–292Google Scholar
  96. 96.
    Bicikova M, Szamel I, Hill M, Tallova J, Starka L, 2001 Allopregnanolone, pregnenolone sulphate and epitestosterone in breast cyst fluid Steroids 66: 55–57PubMedGoogle Scholar
  97. 97.
    Chasalow FI, Bradlow HL, 1990 Digoxin-like materials in human breast cyst fluids Ann NY Acad Sci 586: 107–116PubMedGoogle Scholar
  98. 98.
    Chasalow FI, Blethen SL, 1990 Characterization of digoxin-like materials in human cord serum Ann NY Acad Sci 595: 212–221PubMedGoogle Scholar
  99. 99.
    Weber CJ, Kim D, Costanzo M, Morris J, Howe B, Ward L, D’Agati V, McDonald T, O’Dorisio TM, Butler VP Jr., 1994 Relationship of Na and K concentrations to GRP, CGRP and calcitonin immunoreactivities and Na,K-ATPase inhibitory activity in human breast cyst fluid Ann Surg Oncol 1:339–344PubMedGoogle Scholar
  100. 100.
    Bradlow HL, Breed CN, Nisselbaum J, Fleisher M, Schwartz MK, 1987 pH as a marker of breast cyst fluid biochemical type Eur J Surg Oncol 13: 331–334PubMedGoogle Scholar
  101. 101.
    Fleisher M, Breed C, Robbins G, Fracchia A, Urban J, Schwartz M, 1976 The elemental composition of human breast cyst fluids Clin Chem 22: 1213Google Scholar
  102. 102.
    Kanias GD, Kouri E, Arvaniti H, Karaiosifidi H, Kouneli S, 1994 Trace element content in breasts with fibrocystic disease. In: Schrauzer GN Ed., Biological Trace Element Research, Humana Press Inc., Totowa, pp 363–370Google Scholar
  103. 103.
    Troccoli R, Mannello F, 1992 Improved electrophoretic map of breast cyst fluid proteins Cancer Detect Prev 16: 107–112PubMedGoogle Scholar
  104. 104.
    Mannello F, Bocchiotti GD, Stocchi O, Gazzanelli G, 1995 Relationship between α1-acid glycoprotein and electrolyte ratio in human breast cyst fluids Eur J Lab Med 1: 51–54Google Scholar
  105. 105.
    Haagensen DE Jr., Mazoujian G, Dilley WG, Pedersen CE, Kister SJ, Wells SA, 1979 Breast gross cystic disease fluid analysis. I. Isolation and radioimmunoassay for a major component protein J Natl Cancer Inst 62:239–247PubMedGoogle Scholar
  106. 106.
    Dixon JM, Miller WR, Yap PL, Scott WN, Forrest PM, 1983 Further studies on human breast cyst fluids Br J Surg 70: 684Google Scholar
  107. 107.
    Yap PL, Miller WR, Roberts MM, Creel RJ, Freedman B, Mirtle CL, Pryde EAD, McClelland DBL, 1984 Protein concentrations in fluid from gross cystic disease of the breast Clin Oncol 10: 35–43PubMedGoogle Scholar
  108. 108.
    Zangerle PF, Spyratos F, Le Doussal V, Noel G, Hacene K, Hendrick JC, Gest J, Franchimont P, 1986 Breast cyst fluid proteins and breast cancer Ann NY Acad Sci 464: 331–349PubMedGoogle Scholar
  109. 109.
    Balbin M, Vizoso F, Sanchez LM, Venta R, Ruibal A, Fueyo A, Lopez-Otin C, 1991 GCDFP-70 protein in cyst fluid identified as albumin and used to classify cysts in women with breast gross cystic disease Clin Chem 37: 547–551PubMedGoogle Scholar
  110. 110.
    Duncan LJ, Robinson GV, Ghilchik MW, Reed MJ, 1994 The effect of gross cystic disease fluid proteins on oestrogen synthesis in breast cancer cells Endocrine-Related Cancer 2: 27–35Google Scholar
  111. 111.
    Mannello F, Malatesta M, Bocchiotti GD, Gazzanelli G, 1994 α1-Antichymotrypsin complexes in human breast cyst fluids Cancer Lett 76: 155–159PubMedGoogle Scholar
  112. 112.
    Biagioni S, Stella F, Mannello F, Cerroni L, Stella C, Troccoli R, 1985 α1-Antitrypsin, transferrin, alkaline phosphatase, phosphohexoseisomerase and γ-glutamyltransferase in breast cyst fluid Tumori 71: 135–140PubMedGoogle Scholar
  113. 113.
    Pearlman WH, Gueriguian JL, Sawyer ME, 1973 A specific progesterone-binding component of human breast cyst fluid J Biol Chem 248: 5736–5741PubMedGoogle Scholar
  114. 114.
    Pearlman WH, Peng LH, Mazoujian G, Haagensen DE Jr., Wells SA Jr., Kister SJ, 1977 A specific progesterone binding component of human breast cyst fluid: its isolation and characterization J Endocrinol 75: 19–20Google Scholar
  115. 115.
    Dilley WG, Haagensen DE, Cox CE, Wells SA Jr., 1990 Immunologic and steroid binding properties of the GCDFP-24 protein isolated from human breast gross cystic disease fluid Breast Cancer Res Treat 16: 253–260PubMedGoogle Scholar
  116. 116.
    Balbin M, Freije JMP, Fueyo A, Sanchez LM, Lopez-Otin C, 1990 Apolipoprotein D is the major protein component in cyst fluid from women with human breast gross cystic disease Biochem J 271: 803–807PubMedGoogle Scholar
  117. 117.
    Sanchez LM, Diez-Itza I, Vizoso F, Lopez-Otin C, 1992 Cholesterol and apolipoprotein D in gross cystic disease of the breast Clin Chem 38: 695–698PubMedGoogle Scholar
  118. 118.
    Witkin SS, Sarkar NH, Kinne DW, Breed CN, Good RA, Day NK, 1981 Antigens and antibodies cross-reactive to the murine mammary tumor virus in human breast cyst fluids J Clin Invest 67: 216–222PubMedGoogle Scholar
  119. 119.
    Takahashi K, Lai LC, Ghatei MA, James VHT, Bloom SR, 1990 Endothelin-like immunoreactivity in human breast cyst fluid J Clin Endocrinol Metab 71: 1681–1683PubMedGoogle Scholar
  120. 120.
    Lai LC, Ghatei MA, Takahashi K, Patel KV, Schrey MP, Ghilchik MW, Bloom SR, James VHT, 1990 Mitogenic peptides in breast cyst fluid: relationship with intracystic electrolyte ratios Int J Cancer 46: 1014–1016PubMedGoogle Scholar
  121. 121.
    Lai LC, Siraj AK, Kadory S, Lennard TWJ, 1995 Concentrations of soluble vascular cell adhesion molecule-1 and E-selectin in breast cyst fluid and their relation with cyst type Br J Surg 82: 83–85PubMedGoogle Scholar
  122. 122.
    Troccoli R, Stella F, Biagioni S, Battistelli S, Cerroni L, Marcheggiani F, Artico M, Terzano C, Mannello F, 1990 Ferritin and transferrin levels in human breast cyst fluids: relationship with intracystic electrolyte concentrations Clin Chim Acta 192: 1–8PubMedGoogle Scholar
  123. 123.
    Collette J, Hendrick JC, Jaspar JM, Franchimont P, 1986 Presence of α-lactalbumin, epidermal growth factor, epithelial membrane antigen and gross cystic disease fluid protein (15,000 daltons) in breast cyst fluid Cancer Res 46: 3728–3733PubMedGoogle Scholar
  124. 124.
    Mazoujian G, Warhol MJ, Haagensen DE Jr., 1984 The ultrastructural localization of gross cystic disease fluid protein (GCDFP-15) in breast epithelium Am J Pathol 116: 305–310PubMedGoogle Scholar
  125. 125.
    Vandewalle B, Hornez L, Vennin P, Peyrat JP, Lefebvre J, 1986 Further characterization of the light breast cyst fluid protein, GCDFP-15 Biochimie 68: 649–656PubMedGoogle Scholar
  126. 126.
    Haagensen DE Jr., Dilley WG, Mazoujian G, Wells SA Jr., 1990 Review of GCDFP-15 Ann NY Acad Sci 586: 161–173PubMedGoogle Scholar
  127. 127.
    Agrimonti F, Cavallo R, Frairia R, Violino PL, Borretta G, Angeli A, 1982 Immunoglobulin levels in breast cyst fluid: apparent connection with intracystic transcortin binding activity Boll Ist Sieroter Milan 61: 44–50PubMedGoogle Scholar
  128. 128.
    Mannello F, Battistelli S, Bocchiotti GD, Marcheggiani F, Troccoli R, 1991 Circulating immune complexes in human breast cyst fluids: relationship with intracystic immunoglobulin and electrolyte levels Int J Biol Markers 6: 122–127PubMedGoogle Scholar
  129. 129.
    Reed MJ, Coldham NG, Patel SR, Ghilchik MW, James VHT, 1992 Interleukin-1 and interleukin-6 in breast cyst fluid: their role in regulating aromatase activity in breast cancer cells J Endocrinol 132: 5–8Google Scholar
  130. 130.
    Lai LC, Kadory S, Cornell C, Lennard TWJ, 1993 Possible regulation of soluble ICAM-1 levels by interleukin-1 in a subset of breast cysts Int J Cancer 55: 586–589PubMedGoogle Scholar
  131. 131.
    Lai LC, Kadory S, Siraj AK, Lennard TWJ, 1994 Oncostatin, interleukin-2, interleukin-6 and interleukin-8 in breast cyst fluid Int J Cancer 59: 369–372PubMedGoogle Scholar
  132. 132.
    Lai LC, Chan CTM, Cornell C, Lennard TWJ, 1993 Growth inhibitory substances in human breast cyst fluid Anticancer Res 13: 225–228PubMedGoogle Scholar
  133. 133.
    Le Doussal V, Zangerle PF, Collette J, Spyratos F, Hacene K, Briere M, Gest J, Franchimont P. 1984 Immunohistochemical detection of alpha-lactalbumin in breast lesions Eur J Cancer Clin Oncol 20: 1069–1078PubMedGoogle Scholar
  134. 134.
    Miller WR, Dawes J, 1985 Platelet-associated proteins in human breast cyst fluids Clin Chim Acta 152: 37–42PubMedGoogle Scholar
  135. 135.
    Macgregor IR, Miller WR, 1988 Urokinase and tissue-type plasminogen activators are present in breast cyst fluids Eur J Cancer Clin Oncol 24: 985–989PubMedGoogle Scholar
  136. 136.
    Lai LC, Cornell C, Lennard TWJ, 1993 Relationship between oestrogen-inducible proteins, estradiol and electrolyte ratio in breast cyst fluid Cancer Lett 69: 21–25PubMedGoogle Scholar
  137. 137.
    Hayden K, Tetlow L, Byrne G, Bundred N: Radioimmunoassay for the measurement of thrombospondin in plasma and breast cyst fluid: validation and clinical application. Ann Clin Biochem 37: 319–325Google Scholar
  138. 138.
    Frairia R, Agrimonti F, Barbadoro E, Fazzari A, Boccuzzi G, Angeli A, 1983 Evidence for a transcortin-like component in human breast cyst fluid Clin Chim Acta 131: 15–27PubMedGoogle Scholar
  139. 139.
    Haagensen DE, Mazoujian G, 1983 Utilization of the GCDFP-15 protein as a marker of breast carcinomas with apocrine features: clinical and pathological findings Protides Biol Fluids 31: 567–570Google Scholar
  140. 140.
    Haagensen DE, Kelly D, Bodian CA, 1997 GCDFP-15 blood levels for stratification of risk of breast cancer development in women with active breast gross cystic disease Breast 6: 113–119Google Scholar
  141. 141.
    Sapino A, Cassoni P, Bussolati G, 2000 Gross cystic disease fluid protein (GCDFP-15) in the breast: past and present J Biol Regul Homeost Agents 14: 259–262PubMedGoogle Scholar
  142. 142.
    Mannello F, Troccoli R, Battistelli S, Marcheggiani F, 1990 Acid phosphatases in breast cyst fluids Progr Med Lab 4: 473Google Scholar
  143. 143.
    Schwartz MK, Schwartz DC, 1984 Enzyme concentrations in breast cyst fluid and in cytosols of human breast tissue Progr Med Lab 11: 39–40Google Scholar
  144. 144.
    Frame KL, Patton K, Reed MJ, Ghilchik MW, Parish DC, 1996 Angiotensin-converting enzyme and enkephalinase in human breast cyst fluid Br J Cancer 74: 807–813PubMedGoogle Scholar
  145. 145.
    Kesner L, Yu W, Bradlow HL, Breed CW, Fleisher M, 1988 Proteases in cyst fluid from human gross cyst breast disease Cancer Res 48: 6379–6383PubMedGoogle Scholar
  146. 146.
    Scambia G, Benedetti Panici P, Ferrandina G, Battaglia F, Rossi S, Bellantone R, Crucitti F, Mancuso S, 1991 Cathepsin D and epidermal growth factor in human breast cyst fluid Br J Cancer 64: 965–967PubMedGoogle Scholar
  147. 147.
    Banerjee S, Katz J, Levitz M, Finlay TH, 1990 Identification of a novel esterase in human breast cyst fluid Ann NY Acad Sci 586: 204–212PubMedGoogle Scholar
  148. 148.
    Banerjee S, Katz J, Levitz M, Finlay TH, 1991 Purification and properties of an esterase from human breast cyst fluid Cancer Res 51: 1092–1098PubMedGoogle Scholar
  149. 149.
    Levitz M, Raju U, Katz J, Finlay TH, Brind JL, Arcuri F, Castagnetta L, 1992 Esterase activity in human breast cyst fluid: associations with steroid sulphates and cations. Steroids 57: 485–487PubMedGoogle Scholar
  150. 150.
    Magklara A, Scorilas A, Lopez-Otin C, Vizoso F, Ruibal A, Diamandis EP, 1999 Human glandular kallikrein in breast milk, amniotic fluid and breast cyst fluid Clin Chem 45: 1774–1780PubMedGoogle Scholar
  151. 151.
    Minton JP, Walaszek Z, Schooley W, Hanausek-Walaszek M, Webb TE, 1986 β-glucuronidase levels in patients with fibrocystic breast disease Breast Cancer Res Treat 8: 217–222PubMedGoogle Scholar
  152. 152.
    Fleisher M, 1990 The biochemical composition of human breast cyst fluid: the assessment of risk factors for breast cancer Clin Chem 36: 1236Google Scholar
  153. 153.
    Mannello F, Stocchi O, Pazzaglia E, Troccoli R, 1990 γ-glutamyltransferase expression in human breast cyst fluids Progr Med Lab 4: 474Google Scholar
  154. 154.
    Diamandis EP, Yousef GM, Soosaipillai AR, Grass L, Porter A, Little S, Sotiropoulou G., 2000 Immunofluorimetric assay of human kallikrein 6 (zyme, protease M/neurosin) and preliminary clinical applications Clin Biochem 33: 369–375PubMedGoogle Scholar
  155. 155.
    Biagioni S, Mannello F, Stella F, Battistelli S, Marcheggiani F, Cerroni L, Artico M, Terzano C, Troccoli R, 1987. Lactate dehydrogenase, isoenzyme patterns and cation levels in human breast gross cyst fluid Clin Chim Acta 169: 91–98PubMedGoogle Scholar
  156. 156.
    Vizoso F, Allende MT, Fdez Fdez M, Suarez B, Fdez LLana B, Roiz MC, Ruibal A, 1992. Total lactate dehydrogenase and tumor necrosis factor alpha levels in cyst fluid of women with gross cystic breast disease Int J Biol Markers 7: 123–125PubMedGoogle Scholar
  157. 157.
    Mannello F, Bocchiotti GD, Pignatti Morano F, Fratepietro LM, Gazzanelli G, 1996. Lipids status in human breast cyst fluids Cancer Lett 98: 137–143PubMedGoogle Scholar
  158. 158.
    Sanchez LM, Freije JP, Merino AM, Vizoso F, Foltmann B, Lopez-Otin C. 1992. Isolation and characterisation of a pepsin C zymogen produced by human breast tissues J Biol Chem 267: 24725–24731PubMedGoogle Scholar
  159. 159.
    Diamandis EP, Nadkarni S, Bhaumik B, Abdelrahman A, Melegos DN, Borchert G, Black MH, Alonso M, Salas A, de lo Toyos JR, Sampedro A, Lopez-Otin C. 1997. Immunofluorimetric assay of pepsinogen C and preliminary clinical applications Clin Chem 43: 1365–1371PubMedGoogle Scholar
  160. 160.
    Borchert GH, Melegos DN, Yu H, Giai M, Roagna R, Ponzone R, Sgro L, Diamandis EP, 1999. Quantification of pepsinogen C and prostaglandin D synthase in breast cyst fluid and their potential utility for cyst type classification Clin Biochem 32: 39–44PubMedGoogle Scholar
  161. 161.
    Melegos DN, Diamandis EP, Oda H, Urade Y, Hayaishi O, 1996. Immunofluorimetric assay of prostaglandin D synthase in human tissue extracts and fluids Clin Chem 42: 1984–1991PubMedGoogle Scholar
  162. 162.
    Malatesta M, Mannello F, Sebastiani M, Bianchi G, Gazzanelli G, 1999. Prostate-specific antigen found in Type I breast cyst fluids is a secretory product of the apocrine cells lining breast gross cysts Breast Cancer Res Treat 57: 157–163PubMedGoogle Scholar
  163. 163.
    Mannello F, Bocchiotti GD, Bianchi G, Marcheggiani F, Gazzanelli G, 1996. Quantification of prostate-specific antigen immunoreactivity in human breast cyst fluids Breast Cancer Res Treat 38: 247–252PubMedGoogle Scholar
  164. 164.
    Diamandis EP, Yu H, Lopez-Otin C, 1996. Prostate-specific antigen: a new constituent of breast cyst fluid Breast Cancer Res Treat 38: 259–264PubMedGoogle Scholar
  165. 165.
    Lai LC, Erbas H, Lennard TWJ, Peaston RT, 1996. Prostate-specific antigen in breast cyst fluid: possible role of PSA in hormone-dependent breast cancer Int J Cancer 66: 743–746PubMedGoogle Scholar
  166. 166.
    Filella X, Molina R, Alcover J, Carretero P, Ballesta AM, 1996. Detection of nonprostatic PSA in serum and nonserum samples from women Int J Cancer 68: 424–427PubMedGoogle Scholar
  167. 167.
    Filella X, Molina R, Alcover J, Menendez V, Gimenez N, Jo J, Carretero P, Ballesta AM, 1996. Prostate-specific antigen detection by ultrasensitive assay in samples from women Prostate 29: 311–316PubMedGoogle Scholar
  168. 168.
    Mannello F, Sebastiani M, Amati S, Gazzanelli G, 1997. Prostate-specific antigen expression in a case of intracystic carcinoma of the breast: characterisation of immunoreactive protein and literature survey Clin Chem 43:1448–1454PubMedGoogle Scholar
  169. 169.
    Borchert GH, Yu H, Tomlinson G, Giai M, Roagna R, Ponzone R, Sgro L, Diamandis EP, 1999. Prostate-specific antigen molecular forms in breast cyst fluid and serum of women with fibrocystic breast disease J Clin Lab Anal 13: 75–81PubMedGoogle Scholar
  170. 170.
    Mannello F, Malatesta M, Sebastiani M, Gazzanelli G, 2001. Differential distribution of soluble and complexed forms of prostate-specific antigen in cyst fluids of women with gross cystic breast disease J Clin Lab Anal 15: 81–86PubMedGoogle Scholar
  171. 171.
    Mannello F, Gazzanelli G, 2001. Prostate-specific antigen (PSA/hK3): a further player in the field of breast cancer diagnostics? Breast Cancer Res 3: 238–243PubMedGoogle Scholar
  172. 172.
    Diamandis EP, 2000. Prostate-specific antigen: a cancer fighter and a valuable messenger? Clin Chem 46: 896–900PubMedGoogle Scholar
  173. 173.
    Martinez L, Castilla JA, Blanco N, Peran F, Herruzo A, 1995. CA 125, CA 15.3, CA 27.29, CEA, β-hCG and α-fetoprotein levels in cyst fluid of breast macrocysts Int J Gynecol Obstet 48: 187–192Google Scholar
  174. 174.
    Vizoso F, Allende MT, Fueyo A, Vigal G, Garcia-Moran M, Ruibal A, 1989. CA 15.3 behaviour in cystic breast disease Int J Biol Markers 4: 181–182PubMedGoogle Scholar
  175. 175.
    Inaudi P, De Leo V, Baldini S, D’Antona N, 1990. Adrenal steroids and tumor antigens in plasma and cyst fluid of women with gross cystic breast disease Ann NY Acad Sci 586: 117–120PubMedGoogle Scholar
  176. 176.
    Luciani S, Carenza L, Pala A, Amelio G, Cascialli G, Pirozzi F, Pozzi M, Pozzi V, 1990. Evaluation of tumor and trophoblastic marker concentration in breast cyst fluid Ann NY Acad Sci 586: 218–229PubMedGoogle Scholar
  177. 177.
    Fleisher M, Oettgen HF, Breed CN, Robbins GF, Pinsky CM, Schwartz MK, 1974. CEA-like material in fluid from benign cysts of the breast Clin Chem 20: 41–42PubMedGoogle Scholar
  178. 178.
    Olivati S, Cappellari A, Bagarella M, Corradi G, Zago L, Martinelli D, 1986. Carcinoembryonic antigen (CEA) in human breast cyst fluid: a study of 101 cases Ann NY Acad Sci 464: 599Google Scholar
  179. 179.
    Matsuo S, Eto T, Soejima H, Ohara O, Hidaka O, Miyazaki J, Tsunoda T, Kanematsu T, 1993. A case of intracystic carcinoma of the breast: the importance of measuring carcinoembryonic antigen in aspirated cystic fluid Breast Cancer Res Treat 28: 41–44PubMedGoogle Scholar
  180. 180.
    Inaji H, Koyama H, Motomura K, Noguchi S, Tsuji N, Kimura Y, Sato H, Sugano K, Ohkura H, 1994. Simultaneous assay of erbB-2 protein and carcinoembryonic antigen in cyst fluid as an aid in diagnosing cystic lesions of the breast Breast Cancer 1: 25–30PubMedGoogle Scholar
  181. 181.
    Secreto G, Recchione C, Fariselli G, Grignolio E, Di Pietro S, 1984. Circulating levels and breast cyst fluid concentrations of human chorionic gonadotropin, progesterone and testosterone in women with gross cystic breast disease Tumori 70: 523–527PubMedGoogle Scholar
  182. 182.
    Abney TO, Mullins WB, Teran AZ, Greenblatt RB, Mahesh VB, 1988. Fibrocystic breast disease: the significance of β-human chorionic gonadotropin and other polypeptides in breast cyst fluid Fertil Steril 49: 638–643PubMedGoogle Scholar
  183. 183.
    Troccoli R, Battistelli S, Marcheggiani G, Sessa M, Fronduti A, 1990. Levels of human chorionic gonadotropin in breast cyst fluid Int J Biol Markers 5: 133–136PubMedGoogle Scholar
  184. 184.
    Schurz B, Schon HJ, Wenzl R, Kubista E, Spona J, Huber J, 1991. Breast cyst fluid concentrations of β-endorphin, steroids and gonadotropins in premenopausal women with gross cystic disease Maturitas 13: 123–127PubMedGoogle Scholar
  185. 185.
    Enriori PJ, Hirsig RJP, Vico CM, Etkin AE, Negri JC, Enriori CL, 2000. Effect of natural micronized progesterone on the chorionic gonadotropin concentrations in cyst fluids of women with gross cystic breast disease J Steroid Biochem Mol Biol 73: 67–70PubMedGoogle Scholar
  186. 186.
    Mezi S, Reale MG, Aloise G, Marigliani A, Marchei CG, Sallusti E, Mentuccia D, DelNero A, Izzo P, Modesti M, 1999. The intracystic concentration of MCA in the fluid from large breast cysts G Chir 20: 246–251PubMedGoogle Scholar
  187. 187.
    Mannello F, Bocchiotti GD, Troccoli R, 1991. Tissue-polypeptide specific antigen in human breast cyst fluids Eur J Cancer 27 (Suppl 3): S80Google Scholar
  188. 188.
    Alvarez A, Martinez Rodriguez PI, Nunez MI, Alba A, Allende MT, Ruibal AM, 1995. TPS cytosolic levels in non-malignant breast diseases Int J Biol Markers 10: 183–184PubMedGoogle Scholar
  189. 189.
    Vizoso F, Allende MT, Fernandez R, Suarez B, Diez MC, Ruibal A, 1991. High TAG-72 serum levels, defined by MoAb B72.3, in premenopausal women with benign breast disease, are associated with Type I gross cystic disease Int J Biol Markers 6: 197–198PubMedGoogle Scholar
  190. 190.
    Beczassy E, Szamel I, Sulyok Z, Otto S, 2000. Tumour markers in human breast cyst fluid in gross cystic breast disease (GCBD) Magy Onkol 44: 65–67PubMedGoogle Scholar
  191. 191.
    Lai LC, Siraj AK, Erbas H, Lennard TWJ, 1995. Relationship between basic fibroblast growth factor and transforming growth factor-beta 2 in breast cyst fluid J Clin Endocrinol Metab 80: 711–714PubMedGoogle Scholar
  192. 192.
    Jaspar JM, Franchimont P, 1985. Radioimmunoassay of human epidermal growth factor in human breast cyst fluid Eur J Cancer Clin Oncol 21: 1343–1348PubMedGoogle Scholar
  193. 193.
    Lai LC, Dunkley SA, Reed MJ, Ghilchik MW, James VH, 1989. Estradiol and epidermal growth factor in breast cyst fluid Anticancer Res 9: 1853–1856PubMedGoogle Scholar
  194. 194.
    Lai LC, Ghilchik MW, Shaikh NA, Reed MJ, James VHT, 1989. Relationship between epidermal growth factor and dehydroepiandrosterone and its sulphate in breast cyst fluid Br J Cancer 60: 320–323PubMedGoogle Scholar
  195. 195.
    Smith K, Miller WR, Fennelly JA, Matthews JNS, Scott WN, Harris AL, 1989. Quantification of epidermal growth factor in human breast fluids: correlation with dehydroepiandrosterone-sulphate and electrolyte concentrations Int J Cancer 44: 229–232PubMedGoogle Scholar
  196. 196.
    Wang DY, Hamed H, Mockridge CI, Fentiman IS, 1989. Radioimmunoassayable insulin-like growth factor-I in human breast cyst fluid Eur J Cancer Clin Oncol 25: 867–872PubMedGoogle Scholar
  197. 197.
    Boccardo F, Zanardi S, Valenti G, Cannata D, Maisto L, Nicolò G, Barreca A, Del Monte P, Minuto F, 1990. Epidermal growth factor in breast cyst fluids Ann NY Acad Sci 586: 137–142PubMedGoogle Scholar
  198. 198.
    Collette J, Van Cauwenberge JR, Dejardin L, Carlisi A, Jaspar JM, Franchimont P, 1990. Epidermal growth factor and prolactin in human breast cyst fluid: possible correlations with GCDFP-15 Ann NY Acad Sci 586:146–157PubMedGoogle Scholar
  199. 199.
    Lai LC, Dunkley SA, Reed MJ, Ghilchik MW, Shaikh NA, James VHT, 1990. Epidermal growth factor and oestradiol in human breast cyst fluid Eur J Cancer 26: 481–484PubMedGoogle Scholar
  200. 200.
    Tapper D, Gajdusek C, Moe R, Ness J, 1990. Identification of a unique biological tumor marker in human breast cyst fluid and breast cancer tissue Am J Surg 159: 473–478PubMedGoogle Scholar
  201. 201.
    Wang DY, Hamed H, Fentiman IS, 1990, Epidermal growth factor and insulin-like growth factor I in human breast cyst fluid Ann NY Acad Sci 586:158–160PubMedGoogle Scholar
  202. 202.
    Hamed H, Wang DY, Moore JW, Clark GMG, Fentiman IS, 1990. Growth factor and electrolyte concentration in human breast cyst fluid Eur J Cancer 26: 479–480PubMedCrossRefGoogle Scholar
  203. 203.
    Boccardo F, Torrisi R, Zanardi S, Valenti G, Pensa F, De Franchis V, Barreca A, Ferraro P, Minuto F. 1991. EGF in breast cyst fluid: relationships with intracystic androgens, estradiol and progesterone Int J Cancer 47: 523–526PubMedGoogle Scholar
  204. 204.
    Ness JC, Sedghinasab M, Moe RE, Tapper D, 1993. Identification of multiple proliferative growth factors in breast cyst fluid Am J Surg 166: 237–243PubMedGoogle Scholar
  205. 205.
    Hess JC, Sedghinasab M, Moe RE, Pearce LA, Tapper D, 1994. Growth factor profiles in breast cyst fluid identify women with increased breast cancer risk Am J Surg 167: 523–530PubMedGoogle Scholar
  206. 206.
    Zanardi S, Pensa F, Torrisi R, De Franchis V, Barreca A, Minuto F, Boccardo F, 1994. Presence of immunoassayable transforming growth factor-β1 (TGF-β1) in breast cyst fluid (BCF): relationship with the intracystic electrolyte and epidermal growth factor (EGF) content Int J Cancer 59: 725–727PubMedGoogle Scholar
  207. 207.
    Torrisi R, Zanardi S, Pensa F, Valenti G, De Franchis V, Nicolo G, Barreca A, Minuto F, Boccardo F, 1995. Epidermal growth factor content of breast cyst fluid from women with breast cancer or proliferative disease of the breast Breast Cancer Res Treat 33: 219–224PubMedGoogle Scholar
  208. 208.
    Zanardi S, Pensa F, Torrisi R, De Franchis V, Barreca A, Minuto F, Boccardo F, 1996. Presence and distribution of growth factors in breast cyst fluid Ann NY Acad Sci 784: 542–549PubMedGoogle Scholar
  209. 209.
    Boccardo F, Marenghi C, Ghione G, Pepe A, Parodi S, Rubagotti A, 2001. Intracystic epidermal growth factor level is predictive of breast cancer risk in women with gross cystic disease of the breast Int J Cancer 95: 260–265PubMedGoogle Scholar
  210. 210.
    Boccardo F, Lunardi GL, Petti AR, Rubagotti A, 2003. Enterolactone in breast cyst fluid: correlation with EGF and breast cancer risk Breast Cancer Res Treat 79: 17–23PubMedGoogle Scholar
  211. 211.
    Lai LC, Erbas H, Meadows KA, Lennard TWJ, Holly JMP, 1996. Insulin-like growth factor binding protein-3 in breast cyst fluid: relationships with insulin-like growth factors I and II and transforming growth-beta 1 and 2 Cancer Lett 11: 207–212Google Scholar
  212. 212.
    Lai LC, Siraj AK, Erbas H, Lennard TWJ, 1994. Transforming growth factor alpha, beta 1 and beta 2 in breast cyst fluid Anticancer Res 14: 2805–2810PubMedGoogle Scholar
  213. 213.
    Ruibal A, Nunez MI, Schneider J, Del Rio MC, Rabadan F, Tejerina A, 1998 Transforming growth factor beta 2 (TGFbeta2) and dehydroepiandrosterone sulphate (DHEAs) levels in breast macrocyst fluids: different behaviour according to cyst type Int J Biol Markers 13: 173–175PubMedGoogle Scholar
  214. 214.
    Erbas H, Lennard TW, Lai LC, 1999. Latent forms of transforming growth factor-beta 2 (TGF-beta2) in breast cyst fluid Anticancer Res 19: 3077–3082PubMedGoogle Scholar
  215. 215.
    Herruzo A, Castilla JA, Ramirez A, Marcos C, Menjon S, 1999. Tumor necrosis factor-alpha and interleukin-1 and -6 in fibrocystic breast disease Breast Cancer Res Treat 54: 159–164PubMedGoogle Scholar
  216. 216.
    Mannello F, Bocchiotti GD, Troccoli R, Gazzanelli G. 1992. Lipid-associated sialic acid levels in human breast cyst fluids Breast Cancer Res Treat 24: 167–170PubMedGoogle Scholar
  217. 217.
    Baker PR, Reid AD, Siow Y, Preece PE, 1986. Bile acids in human breast cyst fluid Biochem Soc Trans 14: 962–964 Google Scholar
  218. 218.
    Baker PR, Reid AD, Siow Y, Baty JD, Willis RG, 1986. Identification of bile acids in breast cyst fluid Biochem Soc Trans 16: 741–742 Google Scholar
  219. 219.
    Raju U, Levitz M, Javitt NB, 1990. Bile acids in human breast cyst fluid: the identification of lithocholic acid J Clin Endocrinol Metab 70: 1030–1034PubMedGoogle Scholar
  220. 220.
    Javitt NB, Budai K, Miller DG, Cahan AC, Raju U, Levitz M, 1994. Breast-gut connection: origin of chenodeoxycholic acid in breast cyst fluid Lancet 343: 633–635PubMedGoogle Scholar
  221. 221.
    Schon HJ, Schurz B, Wenzl R, Knogler W, Kubista E, 1993 β-endorphin, steroids and prolactin Arch Pathol Lab Med 117: 248–253PubMedGoogle Scholar
  222. 222.
    Mannello F, Bocchiotti GD, Mezzolani MP, Gazzanelli G, 1995. β-endorphin expression in gross cystic breast disease Cancer Lett 89: 189–193PubMedGoogle Scholar
  223. 223.
    Tallova J, Tomandl J, Bicickova M, Simickova M, 2001. Homocysteine in breast cyst fluid Eur J Clin Invest 31: 623–627PubMedGoogle Scholar
  224. 224.
    Zhang SM, Willett WC, Selhub J, Hunter DJ, Giovannucci EL, Holmes MD, Colditz GA, Hankinson SE, 2003. Plasma folate, vitamin B6 and B12, homocysteine and risk of breast cancer J Natl Cancer Inst 95: 373–380PubMedGoogle Scholar
  225. 225.
    Weber CJ, O’Dorisio TM, McDonald TJ, Howe B, Koschitzky T, Merriam L, 1989. Gastrin-releasing peptide-, calcitonin gene-related peptide-, and calcitonin-like immunoreactivity in human breast cyst fluid and gastrin-releasing peptide-like immunoreactivity in human breast carcinoma cell lines Surgery 106: 1134–1140PubMedGoogle Scholar
  226. 226.
    Cassoni P, Sapino A, Haagensen DE, Naldoni C, Bussolati G, 1995. Mitogenic effect of the 15-kDa gross cystic disease fluid protein (GCDFP-15) on breast cancer cell lines and on immortal mammary cells Int J Cancer 60: 216–220PubMedCrossRefGoogle Scholar
  227. 227.
    Arzimanoglou II, Sekeris CE, Vassilaros S, 1988. Absence of in vitro mutagenicity of the fluid from breast cysts of women with macrocystic disease J Cancer Res Clin Oncol 114: 215–216PubMedGoogle Scholar
  228. 228.
    Scott WN, Miller WR, 1991. Mutagens in human breast cyst fluid J Cancer Res Clin Oncol 117: 254–258PubMedGoogle Scholar
  229. 229.
    Mannello F, Sebastiani M, 2003. Zymographic analyses and measurements of matrix metalloproteinase-2 and -9 in nipple aspirate fluids Clin Chem 49: 1546–1550PubMedGoogle Scholar
  230. 230.
    Ohta T, Fukuda M, 2004. Ubiquitin and breast cancer Oncogene 23: 2079–2088PubMedGoogle Scholar
  231. 231.
    Carr KM, Rosenblatt K, Petricoin EF, Liotta LA, 2004. Genomic and proteomic approaches for studying human cancer: prospects for true patient-tailored therapy Human Genomics 1: 134–140PubMedGoogle Scholar
  232. 232.
    Lopez-Otin C, Overall CM, 2002. Protease degradomics: a new challenge for proteomics Nat Rev Mol Cell Biol 3: 509–519PubMedGoogle Scholar
  233. 233.
    Shin BK, Wang H, Hanash S, 2002. Proteomics approaches to uncover the repertoire of circulating biomarkers for breast cancer J Mammary Gland Biol Neoplasia 7: 407–413PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Ferdinando Mannello
    • 1
    • 3
  • Gaetana Anna Maria Tonti
    • 1
  • Stefano Papa
    • 2
  1. 1.Istituto di Istologia ed Analisi di LaboratorioUniversità Studi “Carlo Bo”Urbino (PU)Italy
  2. 2.Istituto di Scienze Morfologiche, Facoltà di Scienze MFNUniversità degli Studi “Carlo Bo”UrbinoItaly
  3. 3.Istituto di Istologia ed Analisi di Laboratorio, Facoltà di Scienze Mat. Fis. Nat.Università Studi “Carlo Bo”,Urbino (PU)Italy

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