Abstract
Background:Here we evaluate the expression and prognostic value of lysozyme, a milk protein that is also synthesized by a significant percentage of breast carcinomas, in women with breast cancer.
Methods:Lysozyme expression was examined by immunohistochemical methods in a series of 177 breast cancer tissue sections. Staining was quantified by using the HSCORE system, which considers both the intensity and the percentage of cells staining at each intensity. The prognostic value of lysozyme was retrospectively evaluated by multivariate analysis that took into account conventional prognostic factors.
Results:A total of 126 of 177 carcinomas (69.4%) stained positive for this protein, but there were clear differences among them with regard to the intensity and percentage of stained cells. Lysozyme values were higher in well-differentiated and moderately differentiated tumors than in poorly differentiated tumors (P < .05). Similarly, lysozyme levels were higher in small and node-negative tumors than in large and node-positive tumors (P < .05). Moreover, results indicated that low lysozyme content predicted shorter relapse-free survival and overall survival (P < .005). Separate Cox multivariate analysis in subgroups of patients as defined by node status showed that lysozyme expression was an independent prognostic factor able to predict both relapse-free survival and overall survival in node-negative patients (P < .05).
Conclusions:Tumoral expression of lysozyme is associated with lesions of favorable evolution in breast cancer. This milk protein may be a new prognostic factor in patients with breast cancer.
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REFERENCES
Fleming A. On a remarkable bacteriolitic element found in tissues and secretions. Proc R Soc London 1922;B93:306–317.
Biggar WD, Sturgess JM. Role of lysozyme in the microbicidal activity of rat alveolar macrophages. Infect Immun 1977;16:974–982.
Klokars ML, Robers P. Stimulation of phagocytosis by human lysozyme. Acta Haematol 1976;52:289–295.
Petrakis NL. Physiologic, biochemical and cytologic aspects of the nipple aspirate fluid. Breast Cancer Res Treat 1986;8:7–19.
Sánchez LM, Vizoso F, Díez-Itza I, López-Otín C. Identification of the major protein components in breast secretions from women with benign and malignant breast diseases. Cancer Res 1992;52:95–100.
Vizoso F, Sánchez LM, Díez-Itza I, Lamelas ML, López-Otín C. Factors affecting protein composition of breast secretions from nonlactating women. Breast Cancer Res Treat 1992;23:251–258.
Vizoso F, Díez-Itza I, Sánchez LM, Ruibal A, López-Otín C. Relationship between prolactin levels and composition of breast secretions in nonlactating women. J Clin Endocrinol Metab 1994;79:525–529.
Bundred NJ, Miller WR, Walker RA. An immunohistochemical study of the tissue distribution of the breast cyst fluid protein Zn-α2-glycoprotein. Histopathology 1987;11:603–610.
Díez-Itza I, Sánchez LM, Allende MT, Vizoso F, Ruibal A, López-Otín C. Zn-alpha2-glycoprotein levels in breast cancer cytosols and correlation with clinical, histological and biochemical parameters. Eur J Cancer 1993;29A:1256–1260.
Díez-Itza I, Vizoso F, Merino AM, et al. Expression and prognostic significance of apolipoprotein D in breast cancer. Am J Pathol 1994;144:310–320.
Mazoujian G, Parish TM, Haagensen DE, Jr. Immunoperoxidase localization of GCDFP-15 with mouse monoclonal antibodies versus rabbit antiserum. J Histochem Cytochem 1988;36:377–382.
Wurster K, Heberling D, Rapp W. Carcinoembryonic antigen (CEA) and lactoferrin (LF) in benign and malignant disease of the breast. A contribution to be immunohistochemical demonstration of marker substances. Geburtshilfe Frauenheilkd 1980;40:412–422.
Charpin C, Lachard A, Poureau-Schneider N. Localization of lactoferrin and nonspecific cross-reacting antigen in human breast carcinomas. Cancer 1985;55:2612–2617.
Simickova M, Lang BA, Rejhar A, Cernoch M, Sakalova J, Pacovsky Z. Immunohistochemical localization of alpha-lactalbumin in human breast cancer tissue. Neoplasma 1989;36:11–20.
Bloom HJG, Richardson WW. Histological grading and prognosis in breast cancer. r J Cancer 1957;11:359–377.
Vaitukaitis JL. Production of antisera with small doses of immunogen: multiple intradermal injections. Methods Enzymol 1981;73:46–52.
McCarty KS, Szabo E, Flowers JL, et al. Use of a monoclonal anti-estrogen receptor antibody in the inmunohistochemical evaluation of human tumors. Cancer Res 1986;46:4244–4248.
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457–481.
Mantel M, Myers M. Problems of convergence of maximum likelihood iterative procedures in multiparameter situations. J Am Stat Assoc 1971;66:484–491.
Cox DR. Regression models and life tables. J R Stat Soc B 1972;34:187–220.
Dixon WJ, Brown MB, Engelman L, et al. BMDP statistical software. Berkeley University of California Press: Berkeley, CA, 1985.
Topper YJ, Freeman CS. Multiple hormone interactions in the developmental biology of the mammary gland. Physiol Rev 1989;60:1049–1106.
Ginsburg E, Vonderhaar BK. Prolactin synthesis and secretion by human breast cancer cells. Cancer Res 1995;55:2591–2595.
Holdaway MI, Friesen HG. Hormone binding by human mammary carcinoma. Cancer Res 1977;37:1946–1952.
Partridge RK, Hahnel R. Prolactin receptors in human breast carcinoma. Cancer 1979;43:643–646.
Turcot Lemay L, Kelly PA. Prolactin in human breast tumors. J Natl Cancer Inst 1982;68:381–383.
Bonneterre J, Peyrat JP, Vandewalle B, Beuscart R, Vie MC, Cappelaere P. Prolactin receptors in human breast cancer. Eur J Cancer Clin Oncol 1982;18:1157–1162.
Touraine F, Martini JF, Zafrani B, et al. Increased expression of prolactin receptor gene assessed by quantitative polymerase chain reaction in human breast tumors versus normal breast tissues. J Clin Endocrinol Metab 1998;83:667–674.
Peyrat JP, Djiane J, Bonneterre J, et al. Stimulation of DNA synthesis by prolactin in human breast tumor explants. Relation to prolactin receptors. Anticancer Res 1984;4:257–262.
Bonneterre J, Peyrat JP, Beuscart R, Demaille A. Biological and clinical aspects of prolactin receptors (PRL-R) in human breast cancer. J Steroid Biochem Mol Biol 1990;37:977–981.
Myal Y, Robinson DB, Iwasiow B, Tsuyuki D, Wong P, Shiu RP. The prolactin-inducible protein (PIP/GCDFP) gene: cloning structure and regulation. Mol Cell Endocrinol 1991;80:165–175.
Fuch G, Wells J. Prolactin receptor antagonists that inhibit the growth of breast cancer cell lines. J Biol Chem 1995;22:13133–13137.
Bontental M, Foekens JA, Lamberts SW, et al. Feasibility, endocrine and anti-tumour effects of a triple endocrine therapy with tamoxifen, a somatostatin analogue and an antiprolactin in post-menopausal metastatic breast cancer: a randomized study with long-term follow-up. Br J Cancer 1998;77:115–122.
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Vizoso, F., Plaza, E., Vázquez, J. et al. Lysozyme Expression by Breast Carcinomas, Correlation With Clinicopathologic Parameters, and Prognostic Significance. Ann Surg Oncol 8, 667–674 (2001). https://doi.org/10.1007/s10434-001-0667-3
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DOI: https://doi.org/10.1007/s10434-001-0667-3