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BMC Cancer
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

Versican but not decorin accumulation is related to malignancy in mammographically detected high density and malignant-appearing microcalcifications in non-palpable breast carcinomas

Authors: Spyros S Skandalis, Vassiliki T Labropoulou, Panagiota Ravazoula, Eleni Likaki-Karatza, Katalin Dobra, Haralabos P Kalofonos, Nikos K Karamanos, Achilleas D Theocharis

Published in: BMC Cancer | Issue 1/2011

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Abstract

Background

Mammographic density (MD) and malignant-appearing microcalcifications (MAMCs) represent the earliest mammographic findings of non-palpable breast carcinomas. Matrix proteoglycans versican and decorin are frequently over-expressed in various malignancies and are differently involved in the progression of cancer. In the present study, we have evaluated the expression of versican and decorin in non-palpable breast carcinomas and their association with high risk mammographic findings and tumor characteristics.

Methods

Three hundred and ten patients with non-palpable suspicious breast lesions, detected during screening mammography, were studied. Histological examination was carried out and the expression of decorin, versican, estrogen receptor α (ERα), progesterone receptor (PR) and c-erbB2 (HER-2/neu) was assessed by immunohistochemistry.

Results

Histological examination showed 83 out of 310 (26.8%) carcinomas of various subtypes. Immunohistochemistry was carried out in 62/83 carcinomas. Decorin was accumulated in breast tissues with MD and MAMCs independently of the presence of malignancy. In contrast, versican was significantly increased only in carcinomas with MAMCs (median ± SE: 42.0 ± 9.1) and MD (22.5 ± 10.1) as compared to normal breast tissue with MAMCs (14.0 ± 5.8), MD (11.0 ± 4.4) and normal breast tissue without mammographic findings (10.0 ± 2.0). Elevated levels of versican were correlated with higher tumor grade and invasiveness in carcinomas with MD and MAMCs, whereas increased amounts of decorin were associated with in situ carcinomas in MAMCs. Stromal deposition of both proteoglycans was related to higher expression of ERα and PR in tumor cells only in MAMCs.

Conclusions

The specific accumulation of versican in breast tissue with high MD and MAMCs only in the presence of malignant transformation and its association with the aggressiveness of the tumor suggests its possible use as molecular marker in non-palpable breast carcinomas.
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Literature
1.
Colbert JA, Kaine EM, Bigby J, Smith DN, Moore RH, Rafferty E, Georgian-Smith D, Anne D'Alessandro H, Yeh E, Kopans DB, Halpern EF, Hughes K, et al: The age at which women begin mammographic screening. Cancer. 2004, 101: 1850-1859. 10.1002/cncr.20583.CrossRefPubMed
2.
Tabar L, Yen MF, Vitak B, Chen HHT, Smith RA, Duffy SW: Mammography service screening and mortality in breast cancer patients: 20-year follow-up before and after introduction of screening. Lancet. 2003, 361: 1405-1410. 10.1016/S0140-6736(03)13143-1.CrossRefPubMed
3.
Ernst MF, Voogd AC, Coebergh JW, Roukema JA: Breast carcinoma diagnosis, treatment, and prognosis before and after the introduction of mass mammographic screening. Cancer. 2004, 100: 1337-1344. 10.1002/cncr.20139.CrossRefPubMed
4.
Burstein HJ, Polyak K, Wong JS, Lester SC, Kaelin CM: Ductal carcinoma in situ of the breast. N Engl J Med. 2004, 350: 1430-1441. 10.1056/NEJMra031301.CrossRefPubMed
5.
Boyd NF, Guo H, Martin LJ, Sun L, Stone J, Fishell E, Jong RA, Hislop G, Chiarelli A, Minkin S, Yaffe MJ: Mammographic density and the risk and detection of breast cancer. N Engl J Med. 2007, 356: 227-236. 10.1056/NEJMoa062790.CrossRefPubMed
6.
Vachon CM, van Gils CH, Sellers TA, Ghosh K, Pruthi S, Brandt KR, Pankratz VS: Mammographic density, breast cancer risk and risk prediction. Breast Cancer Res. 2007, 9: 217-10.1186/bcr1829.CrossRefPubMedPubMedCentral
7.
Lee NA, Rusinek H, Weinreb J, Chandra R, Toth H, Singer C, Newstead G: Fatty and fibroglandular tissue volumes in the breasts of women 20-83 years old: comparison of X-ray mammography and computer-assisted MR imaging. AJR Am J Roentgenol. 1997, 168: 501-506.CrossRefPubMed
8.
Martin LJ, Boyd NF: Potential mechanisms of breast cancer risk associated with mammographic density: hypotheses based on epidemiological evidence. Breast Cancer Res. 2008, 10: 201-10.1186/bcr1831.CrossRefPubMedPubMedCentral
9.
Kerlikowske K, Smith-Bidman R, Ljung B-M, Grady D: Evaluation of abnormal mammography results and palpable breast abnormalities. Ann Intern Med. 2003, 139: 274-284.CrossRefPubMed
10.
Tse GM, Tan PH, Cheung HS, Chu WC, Lam WW: Intermediate to highly suspicious calcification in breast lesions: a radio-pathologic correlation. Breast Cancer Res Treat. 2008, 110: 1-7. 10.1007/s10549-007-9695-4.CrossRefPubMed
11.
Roubidoux MA, Bailey JE, Wray LA, Helvie MA: Invasive cancers detected after breast cancer screening yielded a negative result: relationship of mammographic density to tumor prognostic factors. Radiology. 2004, 230: 42-48. 10.1148/radiol.2301020589.CrossRefPubMed
12.
Karamouzis MV, Likaki-Karatza E, Ravazoula P, Badra FA, Koukouras D, Tzorakoleftherakis E, Papavassiliou AG, Kalofonos HP: Non-palpable breast carcinomas: correlation of mammographically detected malignant-appearing microcalcifications and molecular prognostic factors. Int J Cancer. 2002, 102: 86-90. 10.1002/ijc.10654.CrossRefPubMed
13.
Badra FA, Karamouzis MV, Ravazoula P, Likaki-Karatza E, Tzorakoleftherakis E, Koukouras D, Iconomou G, Xiros N, Siablis D, Papavassiliou AG, Kalofonos HP: Non-palpable breast carcinomas: correlation of mammographically detected malignant-appearing microcalcifications and epidermal growth factor receptor (EGFR) family expression. Cancer Lett. 2006, 244: 34-41. 10.1016/j.canlet.2005.11.047.CrossRefPubMed
14.
15.
Weigel MT, Dowsett M: Current and emerging biomarkers in breast cancer: prognosis and prediction. Endocr Relat Cancer. 2010, 17: R245-262. 10.1677/ERC-10-0136.CrossRefPubMed
16.
Lelièvre SA, Weaver VM, Nickerson JA, Larabell CA, Bhaumik A, Petersen OW, Bissell MJ: Tissue phenotype depends on reciprocal interactions between the extracellular matrix and the structural organization of the nucleus. Proc Natl Acad Sci USA. 1998, 95: 14711-14716. 10.1073/pnas.95.25.14711.CrossRefPubMedPubMedCentral
17.
Spencer VA, Xu R, Bissell MJ: Gene expression in the third dimension: the ECM-nucleus connection. J Mammary Gland Biol Neoplasia. 2010, 15: 65-71. 10.1007/s10911-010-9163-3.CrossRefPubMedPubMedCentral
18.
Ricciardelli C, Mayne K, Sykes PJ, Raymond WA, McCaul K, Marshall VR, Horsfall DJ: Elevated levels of versican but not decorin predict disease progression in early-stage prostate cancer. Clin Cancer Res. 1998, 4: 963-971.PubMed
19.
Sakko AJ, Ricciardelli C, Mayne K, Tilley WD, LeBaron RG, Horsfall DJ: Versican accumulation in human prostatic fibroblast cultures is enhanced by prostate cancer cell-derived transforming growth factor beta1. Cancer Res. 2001, 61: 926-930.PubMed
20.
Nara Y, Kato Y, Torii Y, Tsuji Y, Nakagaki S, Goto S, Isobe H, Nakashima N, Takeuchi J: Immunohistochemical localization of extracellular matrix components in human breast tumours with special reference to PG-M ⁄ versican. Histochem J. 1997, 29: 21-30. 10.1023/A:1026460700592.CrossRefPubMed
21.
Ricciardelli C, Brooks JH, Suwiwat S, Sakko AJ, Mayne K, Raymond WA, Seshadri R, LeBaron RG, Horsfall DJ: Regulation of stromal versican expression by breast cancer cells and importance to relapse-free survival in patients with node-negative primary breast cancer. Clin Cancer Res. 2002, 8: 1054-1060.PubMed
22.
Theocharis AD, Vynios DH, Papageorgakopoulou N, Skandalis SS, Theocharis DA: Altered content composition and structure of glycosaminoglycans and proteoglycans in gastric carcinoma. Int J Biochem Cell Biol. 2003, 35: 376-390. 10.1016/S1357-2725(02)00264-9.CrossRefPubMed
23.
Tsara ME, Theocharis AD, Theocharis DA: Compositional and structural alterations of proteoglycans in human rectum carcinoma with special reference to versican and decorin. Anticancer Res. 2002, 22: 2893-2898.PubMed
24.
Theocharis AD: Human colon adenocarcinoma is associated with specific post-translational modifications of versican and decorin. Biochim Biophys Acta. 2002, 1588: 165-172.CrossRefPubMed
25.
Voutilainen K, Anttila M, Sillanpää S, Tammi R, Tammi M, Saarikoski S, Kosma VM: Versican in epithelial ovarian cancer: relation to hyaluronan, clinicopathologic factors and prognosis. Int J Cancer. 2003, 107: 359-364. 10.1002/ijc.11423.CrossRefPubMed
26.
Skandalis SS, Kletsas D, Kyriakopoulou D, Stavropoulos M, Theocharis DA: The greatly increased amounts of accumulated versican and decorin with specific post-translational modifications may be closely associated with the malignant phenotype of pancreatic cancer. Biochim Biophys Acta. 2006, 1760: 1217-1225.CrossRefPubMed
27.
Skandalis SS, Theocharis AD, Papageorgakopoulou N, Vynios DH, Theocharis DA: The increased accumulation of structurally modified versican and decorin is related with the progression of laryngeal cancer. Biochimie. 2006, 88: 1135-1143. 10.1016/j.biochi.2006.03.011.CrossRefPubMed
28.
Skandalis SS, Theocharis AD, Theocharis DA, Papadas T, Vynios DH, Papageorgakopoulou N: Matrix proteoglycans are markedly affected in advanced laryngeal squamous cell carcinoma. Biochim Biophys Acta. 2004, 1689: 152-161.CrossRefPubMed
29.
Labropoulou VT, Theocharis AD, Ravazoula P, Perimenis P, Hjerpe A, Karamanos NK, Kalofonos HP: Versican but not decorin accumulation is related to metastatic potential and neovascularization in testicular germ cell tumours. Histopathology. 2007, 49: 582-593.CrossRef
30.
Theocharis AD: Versican in health and disease. Connect Tissue Res. 2008, 49: 230-234. 10.1080/03008200802147571.CrossRefPubMed
31.
Wight TN: Versican: a versatile extracellular matrix proteoglycan in cell biology. Curr Opin Cell Biol. 2002, 14: 617-623. 10.1016/S0955-0674(02)00375-7.CrossRefPubMed
32.
Theocharis AD, Skandalis SS, Tzanakakis GN, Karamanos NK: Proteoglycans in health and disease: novel roles for proteoglycans in malignancy and their pharmacological targeting. FEBS J. 2010, 277: 3904-3923. 10.1111/j.1742-4658.2010.07800.x.CrossRefPubMed
33.
Leygue E, Snell L, Dotzlaw H, Troup S, Hiller-Hitchcock T, Murphy LC, Roughley PJ, Watson PH: Lumican and decorin are differentially expressed in human breast carcinoma. J Pathol. 2000, 192: 313-320. 10.1002/1096-9896(200011)192:3<313::AID-PATH694>3.0.CO;2-B.CrossRefPubMed
34.
Troup S, Njue C, Kliewer EV, Parisien M, Roskelley C, Chakravarti S, Roughley PJ, Murphy LC, Watson PH: Reduced expression of the small leucine-rich proteoglycans, lumican and decorin is associated with poor outcome in node-negative invasive breast cancer. Clin Cancer Res. 2003, 9: 207-214.PubMed
35.
Kelemen LE, Couch FJ, Ahmed S, Dunning AM, Pharoah PD, Easton DF, Fredericksen ZS, Vierkant RA, Pankratz VS, Goode EL, Scott CG, Rider DN, et al: Genetic variation in stromal proteins decorin and lumican with breast cancer: investigations in two case-control studies. Breast Cancer Res. 2008, 10: R98-10.1186/bcr2201.CrossRefPubMedPubMedCentral
36.
Mesurolle B, Ariche-Cohen M, Mignon F, Goumot PA: Clustering of breast microcalcifications on digital mammography: which parameters?. Clin Radiol. 2002, 57: 75-76. 10.1053/crad.2001.0694.CrossRefPubMed
37.
de Paredes ES, Langer TG, Cousins J: Interventional breast procedures. Curr Probl Diagn Radiol. 1998, 27: 133-184.CrossRefPubMed
38.
Alowami S, Troup S, Al-Haddad S, Kirkpatrick I, Watson PH: Mammographic density is related to stroma and stromal proteoglycan expression. Breast Cancer Res. 2003, 5: R129-R135. 10.1186/bcr622.CrossRefPubMedPubMedCentral
39.
Friedenreich CM, Bryant HE, Alexander F, Hugh J, Danyluk J, Page DL: Risk factors for benign breast biopsies: a nested case-control study in the Alberta breast screening program. Cancer Detect Prev. 2001, 25: 280-291.PubMed
40.
Guo YP, Martin LJ, Hanna W, Banerjee D, Miller N, Fishell E, Khokha R, Boyd NF: Growth factors and stromal matrix proteins associated with mammographic densities. Cancer Epidemiol Biomarkers Prev. 2001, 10: 243-248.PubMed
41.
Thurfjell E: Breast density and the risk of breast cancer. N Engl J Med. 2002, 347: 866-10.1056/NEJMp020093.CrossRefPubMed
42.
Lochter A, Bissell MJ: Involvement of extracellular matrix constituents in breast cancer. Semin Cancer Biol. 1995, 6: 165-173. 10.1006/scbi.1995.0017.CrossRefPubMed
43.
Kurose K, Hoshaw-Woodard S, Adeyinka A, Lemeshow S, Watson PH, Eng C: Genetic model of multi-step breast carcinogenesis involving the epithelium and stroma: clues to tumour-microenvironment interactions. Hum Mol Genet. 2001, 10: 1907-1913. 10.1093/hmg/10.18.1907.CrossRefPubMed
44.
Kurose K, Gilley K, Matsumoto S, Watson PH, Zhou XP, Eng C: Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas. Nat Genet. 2002, 32: 355-357. 10.1038/ng1013.CrossRefPubMed
45.
Kinzler KW, Vogelstein B: Landscaping the cancer terrain. Science. 1998, 280: 1036-1037. 10.1126/science.280.5366.1036.CrossRefPubMed
46.
Byrne C, Schairer C, Brinton LA, Wolfe J, Parekh N, Salane M, Carter C, Hoover R: Effects of mammographic density and benign breast disease on breast cancer risk (United States). Cancer Causes Control. 2001, 12: 103-110. 10.1023/A:1008935821885.CrossRefPubMed
47.
Goldoni S, Iozzo RV: Tumor microenvironment: modulation by decorin and related molecules harboring leucine-rich tandem motifs. Int J Cancer. 2008, 123: 2473-2479. 10.1002/ijc.23930.CrossRefPubMed
48.
Misra S, Heldin P, Hascall VC, Karamanos NK, Skandalis SS, Markwald RR, Ghatak S: Hyaluronan-CD44 interactions as potential targets for cancer therapy. FEBS J. 2011, 10.1111/j.1742-4658.2011.08071.x..
49.
Yee AJ, Akens M, Yang BL, et al: The effect of versican G3 domain on local breast cancer invasiveness and bony metastasis. Breast Cancer Res. 2007, 9: R47-10.1186/bcr1751.CrossRefPubMedPubMedCentral
50.
Johansson H, Gandini S, Bonanni B, Mariette F, Guerrieri-Gonzaga A, Serrano D, Cassano E, Ramazzotto F, Baglietto L, Sandri MT, Decensi A: Relationships between circulating hormone levels, mammographic percent density and breast cancer risk factors in postmenopausal women. Breast Cancer Res Treat. 2008, 108: 57-67. 10.1007/s10549-007-9577-9.CrossRefPubMed
51.
Vachon CM, Sasano H, Ghosh K, Brandt KR, Watson DA, Reynolds C, Lingle WL, Goss PE, Li R, Aiyar SE, Scott CG, Pankratz VS, et al: Aromatase immunoreactivity is increased in mammographically dense regions of the breast. Breast Cancer Res Treat. 2011, 125: 243-252. 10.1007/s10549-010-0944-6.CrossRefPubMed
52.
Kousidou OCh, Berdiaki A, Kletsas D, Zafiropoulos A, Theocharis AD, Tzanakakis GN, Karamanos NK: Estradiol-estrogen receptor: a key interplay of the expression of syndecan-2 and metalloproteinase-9 in breast cancer cells. Mol Oncol. 2008, 2: 223-232. 10.1016/j.molonc.2008.06.002.CrossRefPubMed
53.
Rickard DJ, Monroe DG, Ruesink TJ, Khosla S, Riggs BL, Spelsberg TC: Phytoestrogen genistein acts as an estrogen agonist on human osteoblastic cells through estrogen receptors alpha and beta. J Cell Biochem. 2003, 89: 633-646. 10.1002/jcb.10539.CrossRefPubMed
54.
Yanaihara A, Otsuka Y, Iwasaki S, Aida T, Tachikawa T, Irie T, Okai T: Differences in gene expression in the proliferative human endometrium. Fertil Steril. 2005, 83 (Suppl 1): 1206-1215.CrossRefPubMed
55.
Morgan MP, Cooke MM, McCarthy GM: Microcalcifications associated with breast cancer: an epiphenomenon or biologically significant feature of selected tumors?. J Mammary Gland Biol Neopl. 2005, 10: 181-187. 10.1007/s10911-005-5400-6.CrossRef
56.
Rees SG, Shellis RP, Embery G: Inhibition of hydroxyapatite crystal growth by bone proteoglycans and proteoglycan components. Biochem Biophys Res Commun. 2002, 292: 727-733. 10.1006/bbrc.2002.6699.CrossRefPubMed
57.
Theocharis AD, Seidel C, Borset M, Dobra K, Baykov V, Labropoulou V, Kanakis I, Dalas E, Karamanos NK, Sundan A, Hjerpe A: Serglycin constitutively secreted by myeloma plasma cells is a potent inhibitor of bone mineralization in vitro. J Biol Chem. 2006, 281: 35116-35128. 10.1074/jbc.M601061200.CrossRefPubMed
58.
Waddington RJ, Roberts HC, Sugars RV, Schonherr E: Differential roles for small leucine-rich proteoglycans in bone formation. Eur Cell Mater. 2003, 6: 12-21. discussion 21PubMed
59.
Fischer JW, Steitz SA, Johnson PY, Burke A, Kolodgie F, Virmani R, Giachelli C, Wight TN: Decorin promotes aortic smooth muscle cell calcification and colocalizes to calcified regions in human atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2004, 24: 2391-2396. 10.1161/01.ATV.0000147029.63303.28.CrossRefPubMed
60.
Azari F, Vali H, Guerquin-Kern JL, Wu TD, Croisy A, Sears SK, Tabrizian M, McKee MD: Intracellular precipitation of hydroxyapatite mineral and implications for pathologic calcification. J Struct Biol. 2008, 162: 468-479. 10.1016/j.jsb.2008.03.003.CrossRefPubMed
61.
Morgan M, Cooke M, Christopherson P, Westfall P, McCarthy G: Calcium hydroxyapatite promotes mitogenesis and matrix metalloproteinase expression in human breast cancer cell lines. Mol Carcinog. 2001, 32: 111-117. 10.1002/mc.1070.CrossRefPubMed
62.
McCarthy GM, Augustine JA, Baldwin AS, Christopherson PA, Cheung HS, Westfall PR, Scheinman RI: Molecular mechanisms of basic calcium phosphate crystal-induced activation of human fibroblasts. J Biol Chem. 1998, 273: 35161-35169. 10.1074/jbc.273.52.35161.CrossRefPubMed
63.
McCarthy G, Mitchell P, Cheung H: The mitogenic response to stimulation with basic calcium phosophate crystals is accompanied by induction and secretion of collagenase in human fibroblasts. Arthritis Rheum. 1991, 34: 1021-1030. 10.1002/art.1780340812.CrossRefPubMed
Metadata
Title
Versican but not decorin accumulation is related to malignancy in mammographically detected high density and malignant-appearing microcalcifications in non-palpable breast carcinomas
Authors
Spyros S Skandalis
Vassiliki T Labropoulou
Panagiota Ravazoula
Eleni Likaki-Karatza
Katalin Dobra
Haralabos P Kalofonos
Nikos K Karamanos
Achilleas D Theocharis
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-314

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