Breast Cancer Research and Treatment

, Volume 50, Issue 2, pp 185–191 | Cite as

Monoclonality in fibroadenomas with complex histology and phyllodal features

  • Masako Kasami
  • Cindy L. Vnencak-Jones
  • Suzanne Manning
  • William D. Dupont
  • Roy A. Jensen
  • David L. Page


Fibroadenoma is a common cause of benign breast masses in young women. These women have a slightly increased risk of subsequent breast cancer, particularly if their tumors have complex histologic patterns. We assessed monoclonality in fibroadenomas and correlated the results with histologic analysis. We performed a clonal analysis of 52 fibroadenomas from 43 patients using X-chromosome inactivation studies. The cases included fibroadenomas with complex and simple histology. Areas examined were predominantly stroma but epithelium was also present. DNA was isolated from paraffin-embedded tissue and was subjected to polymerase chain reaction amplification of the human androgen receptor gene with and without predigestion of the DNA with Hha 1. If a monoclonal process was identified, the epithelial and stromal components were subsequently microdissected and reanalyzed. 36/43 (83.7%) women were heterozygous. We studied 45 tumors in these 36 informative women. 1/20 (5% complex fibroadenomas and 1/25 (4%) simple fibroadenomas were monoclonal. The epithelial component of both monoclonal fibroadenomas was polyclonal. The one monoclonal simple fibroadenoma was also the only one with mixed features to contain a phyllodes component. In this case, monoclonality was found in the stroma of both the fibroadenoma and phyllodes regions. Monoclonality has been previously associated with phyllodes phenotype, but not with fibroadenomas, except for 3 fibroadenomas that recurred as phyllodes tumor. We report that monoclonality may also be seen occasionally in complex fibroadenomas, and was found in a tumors with mixed fibroadenoma/phyllodes features without clinical recurrence for 4 years.

breast fibroadenoma human androgen receptor gene monoclonality X-chromosome inactivation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Dupont WD, Page DL: Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med 312: 146–151, 1985Google Scholar
  2. 2.
    Dupont WD, Page DL, Parl FF, Vnencak-Jones CL, Plummer WDJ, Rados MS, Schuyler PA: Long-term risk of breast cancer in women with fibroadenoma. N Engl J Med 331: 10–15, 1994Google Scholar
  3. 3.
    Rohen C, Staats B, Bonk U, Bartnitzke S, Bullerdiek J: Significance of clonal chromosome aberrations in breast fibroadenomas. Cancer Genet Cytogenet 87: 152–155, 1996Google Scholar
  4. 4.
    Dietrich CU, Pandis N, Teixeira MR, Bardi G, Gerdes A-M, Andersen JA, Heim S: Chromosome abnormalities in benign hyperproliferative disorders of epithelial stromal breast tissue. Int J Cancer 60: 49–53, 1995Google Scholar
  5. 5.
    Fletcher JA, Pinkus GS, Weidner N, Morton CC: Lineage-restricted clonality in biphasic solid tumors. Am J Pathol 138: 1199–1207, 1991Google Scholar
  6. 6.
    Staats B, Bonk U, Wanschura S, Hanisch P, Schoenmakers EFPM, Van de Ven WJM, Bartnitzke S, Bullerdiek J: A fibroadenoma a t(4;12) (q27;q15) affecting the HMGI-C gene, a member of the high mobility group protein gene family. Breast Cancer Res Treat 38: 299–303, 1996Google Scholar
  7. 7.
    Lalle P, De Latour M, Rio P, Bignon Y-J: Detection of allelic losses on 17q12-q21 chromosomal region in benign lesions and malignant tumors occurring in a familial context. Oncogene 9: 437–442, 1994Google Scholar
  8. 8.
    Lizard-Nacol S, Lidereau R, Collin F, Arnal M, Hahnel L, Roignot P, Cuisenier J, Guerrin J: Benign breast disease: Absence of genetic alterations at several loci implicated in breast cancer malignancy. Cancer Res 55: 4416–4419, 1995Google Scholar
  9. 9.
    Noguchi S, Motomura K, Imaji H, Imaoka S, Koyama H: Clonal analysis of fibroadenoma and phyllodes tumor of the breast. Cancer Res 53: 4071–4074, 1993Google Scholar
  10. 10.
    Noguchi S, Yokouchi H, Aihara T, Motomura K, Imaji H, Imaoka S, Koyama H: Progression of fibroadenoma to phylodes tumor demonstrated by clonal analysis. Cancer 76: 1779–1785, 1995Google Scholar
  11. 11.
    Woodruff MFA: Tumor clonality and its biological significance. Adv Cancer Res 50: 197–229, 1988Google Scholar
  12. 12.
    Lyon MF: Sex chromatin and gene action in the mammalian X-chromosome. Am J Hum Genet 14: 135–148, 1962Google Scholar
  13. 13.
    Sukpanichnant S, Vnencak-Jones CL, McCurley TL: Determination of B-cell clonality in paraffin-embedded endoscopic biopsy specimens of abnormal lymphocytic infiltrates and gastrointstinal lymphoma by polymerase chain reaction. Am J Clin Pathol 102: 299–305, 1994Google Scholar
  14. 14.
    Jensen RA, Page DL, Holy JT: Identification of genes expressed in premalignant breast disease by microscopy-dissected cloning. Proc Natl Acad Sci USA 91: 9257–9261, 1994Google Scholar
  15. 15.
    Willman CL, Busque L, Griffith BB, Fevara BE, McClain KL, Duncan MH, Gilliland DG: Langerhans'-cell histiocytosis (histiocytosis X): a clonal proliferative disease. N Engl J Med 331: 154–160, 1994Google Scholar
  16. 16.
    Noguchi S, Aihara T, Motomura K, Imaji H, Imaoka S, Koyama H, Tanaka H: Demonstration of polyclonal origin of giant fibroadenoma of the breast. Virchows Arch 427: 343–347, 1995Google Scholar
  17. 17.
    Malamou-Mitsi VD, Krikoni OC, Agnantis NJ: Clonal analysis by PCR and RFLP in breast cancer and precancerous lesions. Preliminary data. Anticancer Res 16: 3943–3948, 1996Google Scholar
  18. 18.
    Allen RC, Zoghbi HY, Moseley AB, Rosenblatt HM, Belmont JW: Methylation of Hpa II and Hha 1 sites near the polymorphic CAG repeat in the human androgen receptor gene correlates with X-chromosome inactivation. Am J Hum Genet 51: 1229–1239, 1992Google Scholar
  19. 19.
    Tsai YC, Lu Y, Nichols PW, Zlotnikov G, Jones PA, Smith HS: Contiguous patches of normal human mammary epithelium derived from a single stem cell: Implications for breast carcinogenesis. Cancer Res 56: 402–404, 1996Google Scholar
  20. 20.
    Gale RE, Wheadon H, Linch DC: X-chromosome inactivation patterns using HPRT and PKG polymorphisms in hae matologically normal and postchemotherapy females. Br J Haematol 79: 193–197, 1991Google Scholar
  21. 21.
    Mutter GL, Kevin AB: X-chromosome inactivation in the normal female genital tract: implications for identification of neoplasia. Cancer Res 55: 5080–5084, 1995Google Scholar
  22. 22.
    Noguchi S, Motomura K, Inaji H, Imaoka S, Koyama H: Clonal analysis of human breast cancer by means of polymerase chain reaction. Cancer Res 52: 6594–6597, 1992Google Scholar
  23. 23.
    Page DL, Anderson TJ: Diagnostic Histopathology of the Breast. Churchill Livingstone, London, 1987, p 77Google Scholar
  24. 24.
    Stephensen CF, Davis RI, Moore GE, Sandberg AA: Cytogenetic and fluorescence in situ hybridization analysis of breast fibroadenomas. Cancer Genet Cytogenet 63: 32–36, 1992Google Scholar
  25. 25.
    Reid T, Just KE, Holtgreve-Grez H, du Manior S, Speicher MR, Schrock E, Latham C, Blegen H, Zetterberg A, Cremer T, Auer G: Comparative genomic hybridization of formalin-fixed, paraffin-embedded breast tumors reveals different patterns of chromosomal gains and losses in fibroadenoma and diploid and aneuploid carcinomas. Cancer Res 55: 5415–5423, 1995Google Scholar
  26. 26.
    Gaffey MJ, Iezzoni JC, Weiss LM: Clonal analysis of focal nodular hyperplasia of the liver. Am J Pathol 148: 1089–1096, 1996Google Scholar
  27. 27.
    Murry CE, Gipaya CT, Bartosek T, Benditt EP, Schwarz SM: Monoclonality of smooth muscle cells in human atherosclerosis. Am J Pathol 151: 697–705, 1996Google Scholar
  28. 28.
    Tsai YC, Simoneau AR, Spruck CH, Nichols PW, Steven K, Buckley JD, Jones PA: Mosaicism in human epithelium; macroscopic monoclonal patches cover the urothelium. J Urol 153: 1697–1700, 1995Google Scholar

Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • Masako Kasami
    • 1
  • Cindy L. Vnencak-Jones
    • 2
  • Suzanne Manning
    • 2
  • William D. Dupont
    • 3
  • Roy A. Jensen
    • 1
    • 4
  • David L. Page
    • 1
    • 3
  1. 1.Division of Anatomic PathologyUSA
  2. 2.Department of PathologyUSA
  3. 3.Preventive MedicineVanderbilt University Medical CenterNashvilleUSA
  4. 4.Departments of Cell BiologyUSA

Personalised recommendations