Virchows Archiv

, Volume 451, Issue 5, pp 893–897 | Cite as

Immunohistochemical expression of estrogen receptors alpha and beta in lobular neoplasia

  • Aphrodite Nonni
  • Flora Zagouri
  • Theodoros N. Sergentanis
  • Andreas C. Lazaris
  • Efstratios S. Patsouris
  • George C. Zografos
Original Article

Abstract

The designation lobular neoplasia (LN) of the breast includes atypical lobular hyperplasia and lobular carcinoma in situ. Estrogen receptors (ER) play a significant role in breast carcinogenesis. In the present study, ER-alpha and ER-beta status are evaluated in 30 breast tissue specimens from patients whose main lesion was LN. A standard immunohistochemical procedure, using monoclonal antibodies for ER-alpha and ER-beta, was applied to the lesion and the adjacent normal breast tissues, the latter serving as control. In all cases, both receptors were expressed in LN as well as in normal breast ducts and lobules. Concerning ER-alpha, the Allred score and the percentage of ER-alpha-positive cells were significantly higher in LN than in the adjacent normal breast tissue. On the contrary, regarding ER-beta, the Allred score and the percentage of ER-beta-positive cells were significantly lower in LN compared with normal adjacent breast tissue. Greater increase in the percentage of ER-alpha-positive cells was associated with a smaller reduction in the percentage of ER-beta-positive cells and vice versa (Spearman’s rho = −0.5044, p = 0.001). In conclusion, upregulation of ER-alpha and downregulation of ER-beta may represent two discrete molecular events in LN pathogenesis. Of notice, a mutually limiting interaction may exist between the two events.

Keywords

Lobular neoplasia Estrogen receptor Immunohistochemistry Breast 

References

  1. 1.
    Allred DC, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155–168PubMedGoogle Scholar
  2. 2.
    Arpino G, Bardou VJ, Clark GM, Elledge RM (2004) Infiltrating lobular carcinoma of the breast: tumor characteristics and clinical outcome. Breast Cancer Res 6:R149–R156PubMedCrossRefGoogle Scholar
  3. 3.
    Bieche I, Parfait B, Laurendeau I, Girault I, Vidaud M, Lidereau R (2001) Quantification of estrogen receptor alpha and beta expression in sporadic breast cancer. Oncogene 20:8109–8115PubMedCrossRefGoogle Scholar
  4. 4.
    Chi A, Chen X, Chirala M, Younes M (2003) Differential expression of estrogen receptor beta isoforms in human breast cancer tissue. Anticancer Res 23:211–216PubMedGoogle Scholar
  5. 5.
    Cristofanilli M, Gonzalez-Angulo A, Sneige N, Kau SW, Broglio K, Theriault RL, Valero V, Buzdar AU, Kuerer H, Buccholz TA, Hortobagyi GN (2005) Invasive lobular carcinoma classic type: response to primary chemotherapy and survival outcomes. J Clin Oncol 23:41–48PubMedCrossRefGoogle Scholar
  6. 6.
    Frykberg ER (1999) Lobular carcinoma in situ of the breast. Breast J 5:296–303PubMedCrossRefGoogle Scholar
  7. 7.
    Gonzalez-Angulo AM, Sahin A, Krishnamurthy S, Yang Y, Kau SW, Hortobagyi GN, Cristofanilli M (2006) Biologic markers in axillary node-negative breast cancer: differential expression in invasive ductal carcinoma versus invasive lobular carcinoma. Clin Breast Cancer 7:396–400PubMedCrossRefGoogle Scholar
  8. 8.
    Gustafsson JA (1999) Estrogen receptor beta—a new dimension in estrogen mechanism of action. J Endocrinol 163:379–383PubMedCrossRefGoogle Scholar
  9. 9.
    Jarvinen TA, Pelto-Huikko M, Holli K, Isola J (2000) Estrogen receptor beta is coexpressed with ERalpha and PR and associated with nodal status, grade, and proliferation rate in breast cancer. Am J Pathol 156:29–35PubMedGoogle Scholar
  10. 10.
    Lakhani SR, Audretsch W, Cleton-Jensen AM, Cutuli B, Ellis I, Eusebi V, Greco M, Houslton RS, Kuhl CK, Kurtz J, Palacios J, Peterse H, Rochard F, Rutgers E, EUSOMA (2006) The management of lobular carcinoma in situ (LCIS). Is LCIS the same as ductal carcinoma in situ (DCIS). Eur J Cancer 42:2205–2211PubMedCrossRefGoogle Scholar
  11. 11.
    Leygue E, Dotzlaw H, Watson PH, Murphy LC (1998) Altered estrogen receptor alpha and beta messenger RNA expression during human breast tumorigenesis. Cancer Res 58:3197–3201PubMedGoogle Scholar
  12. 12.
    Mersin H, Yildirim E, Gulben K, Berberoglu U (2003) Is invasive lobular carcinoma different from invasive ductal carcinoma? Eur J Surg Oncol 29:390–395PubMedCrossRefGoogle Scholar
  13. 13.
    Mohsin SK, O’Connell P, Allred DC, Libby AL (2005) Biomarker profile and genetic abnormalities in lobular carcinoma in situ. Breast Cancer Res Treat 90:249–256PubMedCrossRefGoogle Scholar
  14. 14.
    Morandi L, Marucci G, Foschini MP, Cattani MG, Pession A, Riva C, Eusebi V (2006) Genetic similarities and differences between lobular in situ neoplasia (LN) and invasive lobular carcinoma of the breast. Virchows Arch 449:14–23PubMedCrossRefGoogle Scholar
  15. 15.
    Roger P, Sahla ME, Makela S, Gustafsson JA, Baldet P, Rochefort H (2001) Decreased expression of estrogen receptor beta protein in proliferative preinvasive mammary tumors. Cancer Res 61:2537–2541PubMedGoogle Scholar
  16. 16.
    Sastre-Garau X, Jouve M, Asselain B, Vincent-Salomon A, Beuzeboc P, Dorval T, Durand JC, Fourquet A, Pouillart P (1996) Infiltrating lobular carcinoma of the breast. Clinicopathologic analysis of 975 cases with reference to data on conservative therapy and metastatic patterns.. Cancer 77:113–120PubMedCrossRefGoogle Scholar
  17. 17.
    Schreer I, Luttges J (2005) Precursor lesions of invasive breast cancer. Eur J Radiol 54:62–71PubMedCrossRefGoogle Scholar
  18. 18.
    Shaaban AM, O’Neill PA, Davies MP, Sibson R, West CR, Smith PH, Foster CS (2003) Declining estrogen receptor-beta expression defines malignant progression of human breast neoplasia. Am J Surg Pathol 27:1502–1512PubMedCrossRefGoogle Scholar
  19. 19.
    Shaaban AM, Jarvis C, Moore F, West C, Dodson A, Foster CS (2005) Prognostic significance of estrogen receptor Beta in epithelial hyperplasia of usual type with known outcome. Am J Surg Pathol 29:1593–1599PubMedCrossRefGoogle Scholar
  20. 20.
    Skliris GP, Munot K, Bell SM, Carder PJ, Lane S, Horgan K, Lansdown MR, Parkes AT, Hanby AM, Markham AF, Speirs V (2003) Reduced expression of oestrogen receptor beta in invasive breast cancer and its re-expression using DNA methyl transferase inhibitors in a cell line model. J Pathol 201:213–220PubMedCrossRefGoogle Scholar
  21. 21.
    Speirs V, Skliris GP, Burdall SE, Carder PJ (2002) Distinct expression patterns of ER alpha and ER beta in normal human mammary gland. J Clin Pathol 55:371–374PubMedGoogle Scholar
  22. 22.
    Stygar D, Wang H, Vladic YS, Ekman G, Eriksson H, Sahlin L (2001) Co-localization of oestrogen receptor beta and leukocyte markers in the human cervix. Mol Hum Reprod 7:881–886PubMedCrossRefGoogle Scholar
  23. 23.
    Tong D, Schuster E, Seifert M, Czerwenka K, Leodolte S, Zeillinger R (2002) Expression of estrogen receptor beta isoforms in human breast cancer tissues and cell lines. Breast Cancer Res Treat 71:249–255PubMedCrossRefGoogle Scholar
  24. 24.
    Ulziibat S, Ejima K, Shibata Y, Hishikawa Y, Kitajima M, Fujishita A, Ishimaru T, Koji T (2006) Identification of estrogen receptor beta-positive intraepithelial lymphocytes and their possible roles in normal and tubal pregnancy oviducts. Hum Reprod 21:2281–2289PubMedCrossRefGoogle Scholar
  25. 25.
    Zagouri F, Sergentanis TN, Zografos GC (2007) Precursors and preinvasive lesions of the breast: the role of molecular prognostic markers in the diagnostic and therapeutic dilemma. World J Surg Oncol 5:57PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Aphrodite Nonni
    • 1
  • Flora Zagouri
    • 2
  • Theodoros N. Sergentanis
    • 2
  • Andreas C. Lazaris
    • 1
  • Efstratios S. Patsouris
    • 1
  • George C. Zografos
    • 2
  1. 1.1st Department of Pathology, Medical SchoolUniversity of AthensAthensGreece
  2. 2.Breast Unit, 1st Department of Propaedeutic SurgeryHippokratio Hospital, University of AthensAthensGreece

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