Skip to main content
Journal of Clinical Laboratory Analysis logoLink to Journal of Clinical Laboratory Analysis
. 2001 Mar 30;15(2):81–86. doi: 10.1002/jcla.6

Differential distribution of soluble and complexed forms of prostate‐specific antigen in cyst fluids of women with gross cystic breast disease

Manuela Malatesta 1, Ferdinando Mannello 1,, Maurizio Sebastiani 2, Giancarlo Gazzanelli 1
PMCID: PMC6807965  PMID: 11291110

Abstract

Gross cystic breast disease (GCBD) is the most common benign disease of the human female breast, and patients with GCBD have an increased risk of breast cancer. The aim of this study was to evaluate the distribution inside apocrine cells and in breast cyst fluids aspirated from gross cysts of prostate‐specific antigen (PSA) molecular forms, and to correlate the different intracystic PSA profiles to the subpopulations of gross cysts. Type I cysts showed a median value of 0.71 &mgr;g/L of total PSA and 0.32 g/L of ACT, significantly different to that of Type II cysts (Wilcoxon P < 0.001). Although large excesses of ACT were detected in all samples, BCF samples and apocrine cells from Type I gross cysts contained about 70% of free PSA, compared to the higher amounts of complexed PSA found in Type II gross cysts. We demonstrate that in apocrine/secretive Type I breast gross cysts the serine protease PSA was mainly present in its free form, in contrast to a major proportion of complexed PSA found in flattened/transudative Type II cysts. Our results are consistent with the notion that a prolonged exposure of apocrine breast cells lining the Type I gross cysts to the proteolytic activity of PSA could be involved in the etiopathogenesis of GCBD. J. Clin. Lab. Anal. 15:81–86, 2001. © 2001 Wiley‐Liss, Inc.

Keywords: &agr;1‐antichymotrypsin, biochemistry, breast cyst fluid, electron microscopy, gross cystic breast disease, prostate‐specific antigen

references

  • 1. Haagensen CD. 1986. Disease of the breast. Philadelphia: W.B. Saunders Publisher. [Google Scholar]
  • 2. Love SM, Gelman RS, Silen W. 1982. Fibrocystic disease of the breast: a nondisease? New Engl J Med 307:1010–1014. [DOI] [PubMed] [Google Scholar]
  • 3. Bundred NJ, West RR, Dowd JO, Mansel RE. 1991. Is there an increased risk of breast cancer in womem who have had a breast cyst aspirated? Br J Cancer 64:953–955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4. Bodian CA. 1993. Benign breast diseases, carcinoma in situ, and breast cancer risk. Epidemiol Rev 15:177–187. [DOI] [PubMed] [Google Scholar]
  • 5. Mannello F, Malatesta M, Gazzanelli G. 1999. Breast cancer in women with palpable breast cysts. Lancet 354:677–678. [DOI] [PubMed] [Google Scholar]
  • 6. Bodian CA. 1999. Breast cancer in women with palpable breast cysts. Lancet 354:677. [DOI] [PubMed] [Google Scholar]
  • 7. Molina R, Filella X, Herranz M, et al. 1990. Biochemistry of cyst fluid in fibrocystic disease of the breast: approach to classification and understanding of the mechanism of cyst formation. Ann NY Acad Sci USA 586:29–42. [DOI] [PubMed] [Google Scholar]
  • 8. Angeli A, Dogliotti L, Naldoni C, et al. 1994. Steroid biochemistry and categorization of breast cyst fluid: relation to breast cancer risk. J Steroid Biochem Mol Biol 49:333–339. [DOI] [PubMed] [Google Scholar]
  • 9. Sartorius OW. 1995. The biochemistry of breast cyst fluid and duct secretions. Breast Cancer Res Treat 35:255–266. [DOI] [PubMed] [Google Scholar]
  • 10. Malatesta M, Mannello F, Sebastiani M, et al. 1998. Ultrastructural characterization and biochemical profile of human gross cystic breast disease. Breast Cancer Res Treat 48:211–219, 1998. [DOI] [PubMed] [Google Scholar]
  • 11. Naldoni C, Costantini M, Dogliotti L, et al. 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 52:1791–1795. [PubMed] [Google Scholar]
  • 12. Bruzzi P, Dogliotti L, Naldoni C, et al. 1997. Cohort study of association of risk of breast cancer with cyst type in women with gross cystic disease of the breast. BMJ 314:925–928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Ebbs S, Bates T. 1997. Breast cancer risk with cyst type in cystic disease of the breast. Consistency of cyst type needs to be known. BMJ 315:545. [PMC free article] [PubMed] [Google Scholar]
  • 14. Dixon JM, McDonald C, Elton RA, Miller WR. 1999. Risk of breast cancer in women with palpable breast cysts: a prospective study. Lancet 353:1742–1745. [DOI] [PubMed] [Google Scholar]
  • 15. Yu H, Diamandis EP, Levesque M, et al. 1996. Prostate‐specific antigen in breast cancer, benign breast diseases and normal breast tissue. Breast Cancer Res Treat 40:171–178. [DOI] [PubMed] [Google Scholar]
  • 16. Graves HCB. 1995. Nonprostatic sources of prostatic‐specific antigen: a steroid hormone‐dependent phenomenon? Clin Chem 41:7–9. [PubMed] [Google Scholar]
  • 17. Yu H, Giai M, Diamandis EP, et al. 1995. Prostate‐specific antigen is a new favourable prognostic indicator for women with breast cancer. Cancer Res 55:2104–110. [PubMed] [Google Scholar]
  • 18. Alanen KA, Kuopio T, Collan YU, Kronqvist P, Juntti L, Nevalainen TJ. 1999. Immunohistochemical labelling for prostate‐specific antigen in breast carcinomas. Breast Cancer Res Treat 56:169–176. [DOI] [PubMed] [Google Scholar]
  • 19. Heyl W, Wolff JM, Biesterfeld S, et al. 1999. Immunohistochemical analysis of prostate‐specific antigen does not correlate to other prognostic factors in breast cancer. Anticancer Res 19:2563–565. [PubMed] [Google Scholar]
  • 20. Zaviacic M, Ablin RJ, Ruzickova M, et al. 1999. The normal female and the male breast epithelium does not express prostate‐specific antigen. Preliminary immunohistochemical observations of autopsy breast tissues. Gen Physiol Biophys 18:41–44. [PubMed] [Google Scholar]
  • 21. 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 38:247–252. [DOI] [PubMed] [Google Scholar]
  • 22. Diamandis EP, Yu H, Lopez‐Otin C. 1996. Prostate‐specific antigen: a new constituent of breast cyst fluid. Breast Cancer Res Treat 38:259–264. [DOI] [PubMed] [Google Scholar]
  • 23. Lai LC, Erbas H, Lennard TWJ, Peaston RT. 1996. Prostate‐specific antigen in breast cyst fluid: a possible role of prostate‐specific antigen in hormone‐dependent breast cancer. Int J Cancer 66:743–746. [DOI] [PubMed] [Google Scholar]
  • 24. Borchert GH, Yu H, Tomlinson G, et al. 1999. Prostate‐specific antigen molecular forms in breast cyst fluid and serum of women with fibrocystic breast disease. J Clin Lab Anal 13:75–81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. 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 57:157–163. [DOI] [PubMed] [Google Scholar]
  • 26. 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 21:1047–1050. [DOI] [PubMed] [Google Scholar]
  • 27. Mannello F, Sebastiani M, Amati S, Gazzanelli G. 1997. Prostate‐specific antigen expression in a case of intracystic carcinoma of the breast: characterization of immunoreactive protein and literature surveys. Clin Chem 43:1448–1454. [PubMed] [Google Scholar]
  • 28. Mannello F, Malatesta M, Luchetti F, Papa S, Battistelli S, Gazzanelli G. 1999. Immunoreactivity, ultrastructural localization and transcript expression of prostate‐specific antigen in human neuroblastoma cell lines. Clin Chem 45:78–84. [PubMed] [Google Scholar]
  • 29. Mannello F, Malatesta M, Bocchiotti GD, Gazzanelli G. 1994. &agr;1‐antichymotrypsin complexes in human breast cyst fluids. Cancer Lett 76:155–159. [DOI] [PubMed] [Google Scholar]
  • 30. Mannello F, Troccoli R. 1992. Improved electrophoretic map of breast cyst fluid proteins. Cancer Detect Prev 16:107–112. [PubMed] [Google Scholar]
  • 31. Kesner L, Yu W, Bradlow HL, Breed CW, Fleisher M. 1988. Proteases in cyst fluid from human gross cyst breast disease. Cancer Res 48:6379–6383. [PubMed] [Google Scholar]
  • 32. 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 28:828–832. [DOI] [PubMed] [Google Scholar]
  • 33. Diamandis EP, Yu H. 1995. New biological functions of prostate‐specific antigen. J Clin Endocrinol Metab 80:1515–1517. [DOI] [PubMed] [Google Scholar]
  • 34. Cohen P, Graves HCB, Peehl DM, Kamarei M, Giudice LC. 1992. Prostate‐specific antigen is an insulin‐like growth factor binding protein‐3 protease. J Clin Endocrinol Metab 75:1046–1053. [DOI] [PubMed] [Google Scholar]
  • 35. Killian CS, Corral DA, Kawinsky E, Constantine RI. 1993. Mitogenic response of osteoblast cells to prostate‐specific antigen suggests an activation of latent TGF‐&bgr; and proteolytic modulation of cell adhesion receptors. Biochem Biophys Res Commun 92:940–947. [DOI] [PubMed] [Google Scholar]
  • 36. Yoshida E, Ohmura S, Sugik M, Maruyama M, Mihara H. 1995. Prostate‐specific antigen activates single‐chain urokinase‐type plasminogen activator. Int J Cancer 63:863–865. [DOI] [PubMed] [Google Scholar]
  • 37. Heidtmann HH, Nettelbeck DM, Mingels A, Jager R, Welker HG, Kontermann RE. 1999. Generation of angiostatin‐like fragments from plasminogen by prostate‐specific antigen. Br J Cancer 81:1269–1273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38. Lai LC, Siraj AK, Erbas H, Lennard TWJ. 1994. Transforming growth factor alpha, beta 1 and beta 2 in breast cyst fluid. Anticancer Res 14:2805–2810. [PubMed] [Google Scholar]
  • 39. Leinonen J, Zhang WM, Stenman UH. 1996. Complex formation between PSA isoenzymes and protease inhibitors. J Urol 155:1099–1103. [PubMed] [Google Scholar]
  • 40. Chan DW, Sokoll LJ. 2000. Prostate‐specific antigen: advances and challenges. Clin Chem 45:755–756. [PubMed] [Google Scholar]
  • 41. Diamandis EP. 2000. Prostate‐specific antigen: a cancer fighter and a valuable messenger? Clin Chem 46:896–900. [PubMed] [Google Scholar]

Articles from Journal of Clinical Laboratory Analysis are provided here courtesy of Wiley

RESOURCES