Breast Cancer Research and Treatment

, Volume 112, Issue 3, pp 411–418 | Cite as

Chromosomal aberrations and genetic relations in benign, borderline and malignant phyllodes tumors of the breast: a comparative genomic hybridization study

  • Shuhua Lv
  • Yun Niu
  • Li Wei
  • Qingjie Liu
  • Xiaowei Wang
  • Yan Chen
Preclinical Study


Phyllodes tumors are not quite rare fibroepithelial neoplasms of the breast that show a broad spectrum of clinical behaviour. The molecular genetic features of the heterogenous groups of neoplasms have not been studied in detail yet. We have used comparative genomic hybridization to analyze chromosomal copy number changes in 36 cases of phyllodes tumors (including benign, borderline and malignant phyllodes tumors, 12 cases each). The average number of chromosome copy changes (range) in benign, borderline and malignant phyllodes tumors were 5.58 (0–20), 14.08 (3–23), and 12.42 (0–29) respectively. In benign phyllodes tumors the number of gains and losses was in balance (2.50 vs 3.08), while in borderline and malignant phyllodes tumors gains occurred more often than losses (9.25 vs 4.83, 9.5 vs 2.92). The result suggests the molecular cytogenetics of borderline and malignant phyllodes tumors is similar, and the most striking difference with benign phyllodes tumors is an increased number of chromosomal gains in a nonrandom distribution. Gains of 4q12 seem especially to be involved in the progression of benign to borderline and malignant phyllodes tumors, possibly because of overexpression of oncogenes at these loci.


Breast Chromosome Comparative genomic hybridization Molecular cytogenetics Phyllodes tumors 


  1. 1.
    Bellocq JP, Magro G (2003) Fibroepithelial tumours. In: Tavassoli FA, Devilee P (eds) The WHO classification of tumors of the breast and female genital organs, 1st edn. IARC Press, LyonGoogle Scholar
  2. 2.
    Lv SH, Niu Y (2006) Breast fibroepithelial neoplasms. In: Niu Y (ed) Pathologic diagnostics of breast tumour, 1st edn. Tianjin Science and Technology Press, TianjinGoogle Scholar
  3. 3.
    Granic M, Opric D, Pupic G et al (2006) Surgical methods for the treatment of breast phyllodes tumors-a report of 319 cases. Acta Chir Iugosl 53:57–62PubMedCrossRefGoogle Scholar
  4. 4.
    Moffat CJ, Pinder SE, Dixon AR et al (1995) Phyllodes tumours of the breast: a clinicopathological review of thirty-two cases. Histopathology 27:205–218PubMedCrossRefGoogle Scholar
  5. 5.
    Layfield LJ, Hart J, Neuwirth H et al (1989) Relation between DNA ploidy and the clinical behavior of phyllodes tumors. Cancer 64:1486–1489PubMedCrossRefGoogle Scholar
  6. 6.
    Ribeiro-Silva A, Zambelli Ramalho LN, Zucoloto S (2006) Phyllodes tumor with osteosarcomatous differentiation: a comparative immunohistochemical study between epithelial and mesenchymal cells. Tumori 92:340–346PubMedGoogle Scholar
  7. 7.
    Uriev L, Maslovsky I, Vainshtein P et al (2006) Malignant phyllodes tumor with heterologous liposarcomatous differentiation and tubular adenoma-like epithelial component. Int J Med Sci 3:130–134PubMedGoogle Scholar
  8. 8.
    Kleer CG, Giordano TJ, Braun T et al (2001) Pathologic, immunohistochemical, and molecular features of benign and malignant phyllodes tumors of the breast. Mod Pathol 14:185–190PubMedCrossRefGoogle Scholar
  9. 9.
    Barth RJ Jr (1999) Histologic features predict local recurrence after breast conserving therapy of phyllodes tumors. Breast Cancer Res Treat 57:291–295PubMedCrossRefGoogle Scholar
  10. 10.
    Esposito NN, Mohan D, Brufsky A et al (2006) Phyllodes tumor: a clinicopathologic and immunohistochemical study of 30 cases. Arch Pathol Lab Med 130:1516–1521PubMedGoogle Scholar
  11. 11.
    Noguchi S, Motomura K, Inaji H et al (1993) Clonal analysis of fibroadenoma and phyllodes tumour of the breast. Cancer Res 53:4071–4074PubMedGoogle Scholar
  12. 12.
    Kallioniemi A, Kallioniemi OP, Sudar D et al (1992) Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258:818–821PubMedCrossRefGoogle Scholar
  13. 13.
    Hermsen MA, Meijer GA, Baak JP et al (1996) Comparative genomic hybridization: a new tool in cancer pathology. Hum Pathol 27:342–349PubMedCrossRefGoogle Scholar
  14. 14.
    Hughes S, Williams RD, Webb E et al (2006) Meta-analysis and pooled re-analysis of copy number changes in colorectal cancer detected by comparative genomic hybridization. Anticancer Res 26:3439–3444PubMedGoogle Scholar
  15. 15.
    Ostroverkhova NV, Nazarenko SA, Cheremnykh AD (2002) Comparative genomic hybridization as a new method for detection of genomic imbalance. Genetika 38:149–160PubMedGoogle Scholar
  16. 16.
    Korinth D, Donhuijsen K, Bockmuhl U et al (2004) PHOTOPROBE biotin: an alternative method for labeling archival DNA for comparative genomic hybridization. Cell Oncol 26:329–334PubMedGoogle Scholar
  17. 17.
    Levy B, Hischhorn K (2002) Characterization of constitutional chromosome abnormality by comparative genomic hybridization. In: Fan YS (ed) Methods in molecular-molecular cytogenetics: protocols and applications, Humana Press, TotowaGoogle Scholar
  18. 18.
    Kuijper A, Buerger H, Simon R et al (2002) Analysis of the progression of fibroepithelial tumours of the breast by PCR-based clonality assay. J Pathol 197:575–581PubMedCrossRefGoogle Scholar
  19. 19.
    Dacic S, Kounelis S, Kouri E et al (2002) Immunohistochemical profile of cystosarcoma phyllodes of the breast: a study of 23 cases. Breast J 8:376–381PubMedCrossRefGoogle Scholar
  20. 20.
    Tse GM, Lee CS, Kung FY (2002) Hormonal receptors expression in epithelial cells of mammary phyllodes tumors correlates with pathologic grade of the tumor: a multicenter study of 143 cases. Am J Clin Pathol 118:522–526PubMedCrossRefGoogle Scholar
  21. 21.
    Niu Y, Fu XL, Zhao Y et al (1997) Immunohistochemical study and clinicopathological significance of PCNA in breast phyllodes cystosarcoma. Chin J Pathol 26:337–339Google Scholar
  22. 22.
    Witte F, Honig A, Mirecka J et al (1999) Cystosarcoma phyllodes of the breast: prognostic significance of proliferation and apoptosis associated genes. Anticancer Res 19:3355–3359PubMedGoogle Scholar
  23. 23.
    Chen CM, Chen CJ, Chang CL et al (2000) CD34, CD117, and actin expression in phyllodes tumor of the breast. J Surg Res 94:84–91PubMedCrossRefGoogle Scholar
  24. 24.
    Confavreux C, Lurkin A, Mitton N et al (2006) Sarcomas and malignant phyllodes tumours of the breast—a retrospective study. Eur J Cancer 42:2715–2721PubMedCrossRefGoogle Scholar
  25. 25.
    Yonemori K, Hasegawa T, Shimizu C et al (2006) Correlation of p53 and MIB-1 expression with both the systemic recurrence and survival in cases of phyllodes tumors of the breast. Pathol Res Pract 202:705–712PubMedCrossRefGoogle Scholar
  26. 26.
    Lae M, Vincent-Salomon A, Savignoni A et al (2007) Phyllodes tumors of the breast segregate in two groups according to genetic criteria. Mod Pathol 20:435–444PubMedCrossRefGoogle Scholar
  27. 27.
    Lu YJ, Birdsall S, Osin P et al (1997) Phyllodes tumors of the breast analyzed by comparative genomic hybridization and association of increased 1q copy number with stromal overgrowth and recurrence. Genes Chromosomes Cancer 20:275–281PubMedCrossRefGoogle Scholar
  28. 28.
    Jee KJ, Gong G, Ahn SH (2003) Gain in 1q is a common abnormality in phyllodes tumours of the breast. Anal Cell Pathol 25:89–93PubMedGoogle Scholar
  29. 29.
    Zhang W (2006) A function index of human genes (electronic version)
  30. 30.
    Knuutila S, Bjorkqvist AM, Autio K et al (1998) DNA copy number amplifications in human neoplasms: review of comparative genomic hybridization studies. Am J Pathol 152:1107–1123PubMedGoogle Scholar
  31. 31.
    Tirkkonen M, Tanner M, Karhu R et al (1998) Kallioniemi A, Isola J, Kallioniemi OP: Molecular cytogenetics of primary breast cancer by CGH. Genes Chromosomes Cancer 21:177–184PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Shuhua Lv
    • 1
    • 2
  • Yun Niu
    • 1
  • Li Wei
    • 1
    • 4
  • Qingjie Liu
    • 3
  • Xiaowei Wang
    • 3
  • Yan Chen
    • 3
  1. 1.Breast Cancer Research Key Laboratory of National (Education Ministry), Cancer Institute and HospitalTianjin Medical UniversityTianjinChina
  2. 2.Pathologic DepartmentSecond Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjinChina
  3. 3.Molecular Cytogenetics LaboratoryChinese National Human Genome CenterBeijingChina
  4. 4.Laboratory of Kidney Physician Department, General HospitalTianjin Medical UniversityTianjinChina

Personalised recommendations