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BMC Cancer
Published in: BMC Cancer 1/2008

Open Access 01-12-2008 | Research article

Androgen receptor expresion in breast cancer: Relationship with clinicopathological characteristics of the tumors, prognosis, and expression of metalloproteases and their inhibitors

Authors: Luis O Gonzalez, Maria D Corte, Julio Vazquez, Sara Junquera, Rosario Sanchez, Ana C Alvarez, Juan C Rodriguez, Maria L Lamelas, Francisco J Vizoso

Published in: BMC Cancer | Issue 1/2008

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Abstract

Background

In the present study we analyze, in patients with breast cancer, the tumor expression of androgen receptors (AR), its relationship with clinicopathological characteristics and with the expression of several matrix metalloproteases (MMPs) and their inhibitors (TIMPs), as well as with prognosis.

Methods

An immunohistochemical study was performed using tissue microarrays and specific antibodies against AR, MMPs -1, -2, -7, -9, -11, -13, -14, and TIMPs -1, -2 and -3. More than 2,800 determinations on tumor specimens from 111 patients with primary invasive ductal carcinoma of the breast (52 with axillary lymph node metastases and 59 without them) and controls were performed. Staining results were categorized using a score based on the intensity of the staining and a specific software program calculated the percentage of immunostained cells automatically.

Results

A total of 83 cases (74.8%) showed a positive immunostaining for AR, but with a wide variation in the staining score values. There were no significant associations between the total immunostaining scores for AR and any clinicopathological parameters. However, score values for MMP-1, -7 and -13, were significantly higher in AR-positive tumors than in AR-negative tumors. Likewise, when we considered the cellular type expressing each factor, we found that AR-positive tumors had a higher percentage of cases positive for MMP-1, -7, -11, and TIMP-2 in their malignant cells, as well as for MMP-1 in intratumoral fibroblasts. On the other hand, multivariate analysis demonstrated that patients with AR-positive tumors have a significant longer overall survival than those with AR-negative breast carcinomas (p = 0.03).

Conclusion

Our results confirm that AR are commonly expressed in breast cancer, and are correlated with the expression of some MMPs and TIMP-2. Although we found a specific value of AR expression to be a prognostic indicator in breast cancer, the functional role of AR in these neoplasms is still unclear and further data are needed in order to clarify their biological signification in breast cancer.
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Literature
1.
Kuenen-Boumeester V, Van der Kwast TH, Claassen CC, Look MP, Liem GS, Klijn JG, Henzen-Logmans SC: The clinical significance of androgen receptors in breast cancer and their relation to histological and cell biological parameters. Eur J Cancer. 1996, 32A (9): 1560-1565. 10.1016/0959-8049(96)00112-8.CrossRefPubMed
2.
Nicolas Diaz-Chico B, German Rodriguez F, Gonzalez A, Ramirez R, Bilbao C, Cabrera de Leon A, Aguirre Jaime A, Chirino R, Navarro D, Diaz-Chico JC: Androgens and androgen receptors in breast cancer. J Steroid Biochem Mol Biol. 2007, 105 (1-5): 1-15. 10.1016/j.jsbmb.2006.11.019.CrossRefPubMed
3.
Lippman M, Bolan G, Huff K: The effects of androgens and antiandrogens on hormone-responsive human breast cancer in long-term tissue culture. Cancer Res. 1976, 36 (12): 4610-4618.PubMed
4.
Dorgan JF, Longcope C, Stephenson HE, Falk RT, Miller R, Franz C, Kahle L, Campbell WS, Tangrea JA, Schatzkin A: Relation of prediagnostic serum estrogen and androgen levels to breast cancer risk. Cancer Epidemiol Biomarkers Prev. 1996, 5 (7): 533-539.PubMed
5.
Wysowski DK, Comstock GW, Helsing KJ, Lau HL: Sex hormone levels in serum in relation to the development of breast cancer. Am J Epidemiol. 1987, 125 (5): 791-799.PubMed
6.
Hankinson SE, Willett WC, Manson JE, Colditz GA, Hunter DJ, Spiegelman D, Barbieri RL, Speizer FE: Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women. J Natl Cancer Inst. 1998, 90 (17): 1292-1299. 10.1093/jnci/90.17.1292.CrossRefPubMed
7.
Lillie EO, Bernstein L, Ursin G: The role of androgens and polymorphisms in the androgen receptor in the epidemiology of breast cancer. Breast Cancer Res. 2003, 5 (3): 164-173. 10.1186/bcr593.CrossRefPubMedPubMedCentral
8.
Lea OA, Kvinnsland S, Thorsen T: Improved measurement of androgen receptors in human breast cancer. Cancer Res. 1989, 49 (24 Pt 1): 7162-7167.PubMed
9.
Hall RE, Aspinall JO, Horsfall DJ, Birrell SN, Bentel JM, Sutherland RL, Tilley WD: Expression of the androgen receptor and an androgen-responsive protein, apolipoprotein D, in human breast cancer. Br J Cancer. 1996, 74 (8): 1175-1180.CrossRefPubMedPubMedCentral
10.
Riva C, Dainese E, Caprara G, Rocca PC, Massarelli G, Tot T, Capella C, Eusebi V: Immunohistochemical study of androgen receptors in breast carcinoma. Evidence of their frequent expression in lobular carcinoma. Virchows Arch. 2005, 447 (4): 695-700. 10.1007/s00428-005-0003-6.CrossRefPubMed
11.
Miller WR, Telford J, Dixon JM, Hawkins RA: Androgen receptor activity in human breast cancer and its relationship with oestrogen and progestogen receptor activity. Eur J Cancer Clin Oncol. 1985, 21 (4): 539-542. 10.1016/0277-5379(85)90049-5.CrossRefPubMed
12.
Brentani MM, Franco EL, Oshima CT, Pacheco MM: Androgen, estrogen, and progesterone receptor levels in malignant and benign breast tumors: a multivariate analysis approach. Int J Cancer. 1986, 38 (5): 637-642. 10.1002/ijc.2910380504.CrossRefPubMed
13.
Isola JJ: Immunohistochemical demonstration of androgen receptor in breast cancer and its relationship to other prognostic factors. J Pathol. 1993, 170 (1): 31-35. 10.1002/path.1711700106.CrossRefPubMed
14.
Moinfar F, Okcu M, Tsybrovskyy O, Regitnig P, Lax SF, Weybora W, Ratschek M, Tavassoli FA, Denk H: Androgen receptors frequently are expressed in breast carcinomas: potential relevance to new therapeutic strategies. Cancer. 2003, 98 (4): 703-711. 10.1002/cncr.11532.CrossRefPubMed
15.
Gonzalez LO, Pidal I, Junquera S, Corte MD, Vazquez J, Rodriguez JC, Lamelas ML, Merino AM, Garcia-Muniz JL, Vizoso FJ: Overexpression of matrix metalloproteinases and their inhibitors in mononuclear inflammatory cells in breast cancer correlates with metastasis-relapse. Br J Cancer. 2007, 97 (7): 957-963.PubMedPubMedCentral
16.
Agoff SN, Swanson PE, Linden H, Hawes SE, Lawton TJ: Androgen receptor expression in estrogen receptor-negative breast cancer. Immunohistochemical, clinical, and prognostic associations. Am J Clin Pathol. 2003, 120 (5): 725-731. 10.1309/42F0-0D0D-JD0J-5EDT.CrossRefPubMed
17.
Bieche I, Parfait B, Tozlu S, Lidereau R, Vidaud M: Quantitation of androgen receptor gene expression in sporadic breast tumors by real-time RT-PCR: evidence that MYC is an AR-regulated gene. Carcinogenesis. 2001, 22 (9): 1521-1526. 10.1093/carcin/22.9.1521.CrossRefPubMed
18.
Bratthauer GL, Lininger RA, Man YG, Tavassoli FA: Androgen and estrogen receptor mRNA status in apocrine carcinomas. Diagn Mol Pathol. 2002, 11 (2): 113-118. 10.1097/00019606-200206000-00008.CrossRefPubMed
19.
Gatalica Z: Immunohistochemical analysis of apocrine breast lesions. Consistent over-expression of androgen receptor accompanied by the loss of estrogen and progesterone receptors in apocrine metaplasia and apocrine carcinoma in situ. Pathol Res Pract. 1997, 193 (11-12): 753-758.CrossRefPubMed
20.
Soreide JA, Lea OA, Varhaug JE, Skarstein A, Kvinnsland S: Androgen receptors in operable breast cancer: relation to other steroid hormone receptors, correlations to prognostic factors and predictive value for effect of adjuvant tamoxifen treatment. Eur J Surg Oncol. 1992, 18 (2): 112-118.PubMed
21.
Bayer-Garner IB, Smoller B: Androgen receptors: a marker to increase sensitivity for identifying breast cancer in skin metastasis of unknown primary site. Mod Pathol. 2000, 13 (2): 119-122. 10.1038/modpathol.3880021.CrossRefPubMed
22.
Nelson AR, Fingleton B, Rothenberg ML, Matrisian LM: Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol. 2000, 18 (5): 1135-1149.PubMed
23.
Pang ST, Flores-Morales A, Skoog L, Chuan YC, Nordstedt G, Pousette A: Regulation of matrix metalloproteinase 13 expression by androgen in prostate cancer. Oncol Rep. 2004, 11 (6): 1187-1192.PubMed
24.
Bryan RM, Mercer RJ, Bennett RC, Rennie GC, Lie TH, Morgan FJ: Androgen receptors in breast cancer. Cancer. 1984, 54 (11): 2436-2440. 10.1002/1097-0142(19841201)54:11<2436::AID-CNCR2820541121>3.0.CO;2-H.CrossRefPubMed
25.
Schippinger W, Regitnig P, Dandachi N, Wernecke KD, Bauernhofer T, Samonigg H, Moinfar F: Evaluation of the prognostic significance of androgen receptor expression in metastatic breast cancer. Virchows Arch. 2006, 449 (1): 24-30. 10.1007/s00428-006-0213-6.CrossRefPubMed
26.
27.
Parker RL, Huntsman DG, Lesack DW, Cupples JB, Grant DR, Akbari M, Gilks CB: Assessment of interlaboratory variation in the immunohistochemical determination of estrogen receptor status using a breast cancer tissue microarray. Am J Clin Pathol. 2002, 117 (5): 723-728. 10.1309/PEF8-GL6F-YWMC-AG56.CrossRefPubMed
28.
Vizoso FJ, Gonzalez LO, Corte MD, Rodriguez JC, Vazquez J, Lamelas ML, Junquera S, Merino AM, Garcia-Muniz JL: Study of matrix metalloproteinases and their inhibitors in breast cancer. Br J Cancer. 2007, 96 (6): 903-911. 10.1038/sj.bjc.6603666.CrossRefPubMedPubMedCentral
29.
Narita D, Raica M, Suciu C, Cimpean A, Anghel A: Immunohistochemical expression of androgen receptor and prostate-specific antigen in breast cancer. Folia Histochem Cytobiol. 2006, 44 (3): 165-172.PubMed
30.
Egeblad M, Werb Z: New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002, 2 (3): 161-174. 10.1038/nrc745.CrossRefPubMed
31.
Turk V, Kos J, Turk B: Cysteine cathepsins (proteases)--on the main stage of cancer?. Cancer Cell. 2004, 5 (5): 409-410. 10.1016/S1535-6108(04)00117-5.CrossRefPubMed
32.
Manes S, Llorente M, Lacalle RA, Gomez-Mouton C, Kremer L, Mira E, Martinez AC: The matrix metalloproteinase-9 regulates the insulin-like growth factor-triggered autocrine response in DU-145 carcinoma cells. J Biol Chem. 1999, 274 (11): 6935-6945. 10.1074/jbc.274.11.6935.CrossRefPubMed
33.
Noe V, Fingleton B, Jacobs K, Crawford HC, Vermeulen S, Steelant W, Bruyneel E, Matrisian LM, Mareel M: Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1. J Cell Sci. 2001, 114 (Pt 1): 111-118.PubMed
34.
Fingleton B, Vargo-Gogola T, Crawford HC, Matrisian LM: Matrilysin [MMP-7] expression selects for cells with reduced sensitivity to apoptosis. Neoplasia. 2001, 3 (6): 459-468. 10.1038/sj.neo.7900190.CrossRefPubMedPubMedCentral
35.
Stetler-Stevenson WG: Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention. J Clin Invest. 1999, 103 (9): 1237-1241. 10.1172/JCI6870.CrossRefPubMedPubMedCentral
36.
Cornelius LA, Nehring LC, Harding E, Bolanowski M, Welgus HG, Kobayashi DK, Pierce RA, Shapiro SD: Matrix metalloproteinases generate angiostatin: effects on neovascularization. J Immunol. 1998, 161 (12): 6845-6852.PubMed
37.
Jiang Y, Goldberg ID, Shi YE: Complex roles of tissue inhibitors of metalloproteinases in cancer. Oncogene. 2002, 21 (14): 2245-2252. 10.1038/sj.onc.1205291.CrossRefPubMed
38.
Wurtz SO, Schrohl AS, Sorensen NM, Lademann U, Christensen IJ, Mouridsen H, Brunner N: Tissue inhibitor of metalloproteinases-1 in breast cancer. Endocr Relat Cancer. 2005, 12 (2): 215-227. 10.1677/erc.1.00719.CrossRefPubMed
39.
Gonzalez LO, Corte MD, Junquera S, Bongera M, Rodriguez JC, Vizoso FJ: Expression of androgen receptor and two androgen-induced proteins (apolipoprotein D and pepsinogen C) in ductal carcinoma in situ of the breast. Histopathology. 2007, 50 (7): 866-874. 10.1111/j.1365-2559.2007.02687.x.CrossRefPubMed
40.
Mitropoulou TN, Tzanakakis GN, Kletsas D, Kalofonos HP, Karamanos NK: Letrozole as a potent inhibitor of cell proliferation and expression of metalloproteinases (MMP-2 and MMP-9) by human epithelial breast cancer cells. Int J Cancer. 2003, 104 (2): 155-160. 10.1002/ijc.10941.CrossRefPubMed
41.
Di GH, Lu JS, Song CG, Li HC, Shen ZZ, Shao ZM: Over expression of aromatase protein is highly related to MMPs levels in human breast carcinomas. J Exp Clin Cancer Res. 2005, 24 (4): 601-607.PubMed
42.
Wilson SR, Gallagher S, Warpeha K, Hawthorne SJ: Amplification of MMP-2 and MMP-9 production by prostate cancer cell lines via activation of protease-activated receptors. Prostate. 2004, 60 (2): 168-174. 10.1002/pros.20047.CrossRefPubMed
43.
Miyamoto H, Altuwaijri S, Cai Y, Messing EM, Chang C: Inhibition of the Akt, cyclooxygenase-2, and matrix metalloproteinase-9 pathways in combination with androgen deprivation therapy: potential therapeutic approaches for prostate cancer. Mol Carcinog. 2005, 44 (1): 1-10. 10.1002/mc.20121.CrossRefPubMed
44.
Nielsen BS, Rank F, Lopez JM, Balbin M, Vizoso F, Lund LR, Dano K, Lopez-Otin C: Collagenase-3 expression in breast myofibroblasts as a molecular marker of transition of ductal carcinoma in situ lesions to invasive ductal carcinomas. Cancer Res. 2001, 61 (19): 7091-7100.PubMed
45.
Schneikert J, Peterziel H, Defossez PA, Klocker H, Launoit Y, Cato AC: Androgen receptor-Ets protein interaction is a novel mechanism for steroid hormone-mediated down-modulation of matrix metalloproteinase expression. J Biol Chem. 1996, 271 (39): 23907-23913. 10.1074/jbc.271.39.23907.CrossRefPubMed
46.
Zhou J, Ng S, Adesanya-Famuiya O, Anderson K, Bondy CA: Testosterone inhibits estrogen-induced mammary epithelial proliferation and suppresses estrogen receptor expression. Faseb J. 2000, 14 (12): 1725-1730. 10.1096/fj.99-0863com.CrossRefPubMed
47.
Birrell SN, Bentel JM, Hickey TE, Ricciardelli C, Weger MA, Horsfall DJ, Tilley WD: Androgens induce divergent proliferative responses in human breast cancer cell lines. J Steroid Biochem Mol Biol. 1995, 52 (5): 459-467. 10.1016/0960-0760(95)00005-K.CrossRefPubMed
48.
Buchanan G, Birrell SN, Peters AA, Bianco-Miotto T, Ramsay K, Cops EJ, Yang M, Harris JM, Simila HA, Moore NL, Bentel JM, Ricciardelli C, Horsfall DJ, Butler LM, Tilley WD: Decreased androgen receptor levels and receptor function in breast cancer contribute to the failure of response to medroxyprogesterone acetate. Cancer Res. 2005, 65 (18): 8487-8496. 10.1158/0008-5472.CAN-04-3077.CrossRefPubMed
49.
Beilin J, Ball EM, Favaloro JM, Zajac JD: Effect of the androgen receptor CAG repeat polymorphism on transcriptional activity: specificity in prostate and non-prostate cell lines. J Mol Endocrinol. 2000, 25 (1): 85-96. 10.1677/jme.0.0250085.CrossRefPubMed
Metadata
Title
Androgen receptor expresion in breast cancer: Relationship with clinicopathological characteristics of the tumors, prognosis, and expression of metalloproteases and their inhibitors
Authors
Luis O Gonzalez
Maria D Corte
Julio Vazquez
Sara Junquera
Rosario Sanchez
Ana C Alvarez
Juan C Rodriguez
Maria L Lamelas
Francisco J Vizoso
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2008
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-8-149

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