Subgroups of non-atypical hyperplasia of breast defined by proliferation of oestrogen receptor-positive cells

J Pathol. 2001 Mar;193(3):333-8. doi: 10.1002/1096-9896(2000)9999:9999<::AID-PATH801>3.0.CO;2-#.


In normal breast, there is a negative association between expression of oestrogen receptor (ER) and the proliferation marker Ki67, indicating that ER-positive (ER+) cells do not divide, or that the receptor is down-regulated when they do so. However, dual staining has been found in carcinomas and precancerous lesions, indicating that abnormal regulation of ER could be important in breast tumourigenesis. ER expression in relationship to cell proliferation was studied in 241 foci of hyperplasia of usual type (HUT), a lesion associated with a 1.5 to 2-fold increase in risk of developing breast cancer. Dual label immunofluorescence was employed, using the antibodies 1D5 and Ki67. Two hundred and thirteen foci of HUT contained ER+ cells, which were distributed singly or contiguously and increased with age. Most foci resembled normal breast, but 51 contained dual labelled cells, which did not increase with age. Some of these foci exhibited few, scattered ER+ cells with greater proliferation rates than the ER-negative (ER-) cells, whereas others contained many, contiguous ER+ cells, whose rate of proliferation was less than that of the ER- cells. The latter picture is similar to that which has previously been reported in atypical ductal hyperplasia and ductal carcinoma in situ. The first type of HUT may evolve into the second. The proportion of Ki67+ cells that was ER+ was similar in both types, suggesting a homeostatic mechanism that slows the proliferation of ER+ cells as they become confluent. Overriding this inhibition may be crucial in further progression. Non-atypical hyperplasia is thus heterogeneous in ER expression and proliferation and a significant proportion exhibit abnormal regulation of ER. These findings could have implications for pathological diagnosis, risk assessment, and prophylactic hormonal therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Breast / pathology*
  • Breast Neoplasms / metabolism*
  • Cell Division
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Hyperplasia / metabolism
  • Ki-67 Antigen / metabolism
  • Middle Aged
  • Neoplasm Proteins / metabolism
  • Precancerous Conditions / metabolism*
  • Receptors, Estrogen / metabolism*


  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Neoplasm Proteins
  • Receptors, Estrogen