Relationship of Estrogen and Progesterone Receptor Protein Levels in Carcinomatous and Adjacent Non-Neoplastic Epithelium of the Breast: A Histopathologic and Image Cytometric Study
Background. Results of a previous study demonstrating a correlation between steroid hormone receptor concentrations in benign and tumor tissue in patients with breast carcinoma suggest that receptor levels in breast epithelium undergoing malignant transformation may play a role in determining the receptor levels in the resulting carcinoma. Data used in that study were derived from ligand binding assays and may reflect shortcomings inherent in this methodology, particularly the dilution of receptor proteins from benign and malignant epithelial cells by stromal components.
Methods. We performed a correlation study of steroid hormone receptor expression in benign and malignant breast epithelial cells using computerized image cytometry and histologic sections stained for estrogen (ER) and progesterone receptor (PR), avoiding the problems of contribution of stromal cells to the measurements and uncertainty about the histologic composition of the sample. Sections which contained both tumor and non-neoplastic breast elements were obtained from surgical specimens from 50 patients with breast carcinoma.
Results. Positive area (PA) scores for ER in benign and malignant epithelium showed direct correlation that was significant (r=0.46, p<0.001), whereas those for PR, although trended in the same direction, did not (r=0.17, p>0.2). PA levels for both receptor proteins were higher in benign breast epithelium with proliferative features, compared to non-proliferative benign epithelium, and in tumors when the associated benign tissue had proliferative changes, but neither of these differences were statistically significant, suggesting that the correlation of ER levels in benign and malignant epithelium was not simply a function of proliferative change.
Conclusion. Our results provide support for the concept that ER expression in breast carcinoma depends partially on epithelial cell receptor levels in the breast in which it arises, but not for the analogous hypothesis for PR. When costs and benefits of tamoxifen chemoprevention are weighed for a patient at risk for breast carcinoma, and when cyto- or histopathologic breast tissue specimens are available, it may be reasonable to include breast epithelial ER levels among the factors considered in making the treatment decision.
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- 1.Netto GJ, Cheek JH, Zachariah NY, Romer JC, Lee CF et al.: Steroid receptors in benign mastectomy tissue. Am J Clin Pathol 94: 14-17, 1990Google Scholar
- 2.Khan SA et al.: Estrogen receptor expression of benign breast epithelia and its association with breast carcinoma. Cancer Res 54: 993-997, 1994Google Scholar
- 3.Giani C, D'Amore ED, Delarue JC et al.: Estrogen and progesterone receptors in benign breast tumors and lesions. Relationship with histologic and cytologic features. Int J Cancer 37: 7-10, 1986Google Scholar
- 4.Khan SA, Rogers MAM, Khurana KK, Meguid MM, Numann PJ: Estrogen receptor expression in benign breast epithelium and breast cancer risk. J Nat Cancer Inst 90: 37-42, 1998Google Scholar
- 5.O'Shaughnessy JA: Chemoprevention of breast cancer. JAMA 275: 1349-1353, 1996Google Scholar
- 6.Sukumar S, Carney WP, Barbacid M: Independent molecular pathways in initiation and loss of hormone responsiveness of breastcarcinomas. Science 240: 524-526.Google Scholar
- 7.Pertschuk LP, Kim DS, Nayer K, Feldman JG, Eisenberg KB et al.: Immunocytochemical estrogen and progestin receptor assays in breast cancer with monoclonal antibodies. Histopathologic, demographic, and biochemical correlations and relationship to endocrine response and survival. Cancer 66: 1663-1670, 1990Google Scholar
- 8.Bacus S, Flowers JL, Press MF, Bacus JW, McCarty KS Jr: Evaluation of estrogen receptors in primary breast carcinomas by computer-assisted image analysis. Am J Clin Pathol 90: 233-239, 1988Google Scholar
- 9.Page DL, Anderson TJ: Diagnostic Histopathology of the Breast. New York: Churchill Livingstone, 1987Google Scholar
- 10.Page DL, Dupont WD: Anatomic markers of human premalignancy and risk of breast carcinoma. Cancer 66: 1326-1335, 1990Google Scholar
- 11.Longacre TA, Bartow SA: A correlative morphologic study of human breast and endometrium in the menstrual cycle. Am J Surg Pathol 10: 382-393, 1986Google Scholar
- 12.Anderson TJ, Battersby S, King RJB, McPherson K, Going JJ: Oral contraceptive use influences resting breast proliferation. Human Pathol 20: 1139-1144, 1989Google Scholar
- 13.Henderson BE, Ross RK, Pike MC: Hormonal chemoprevention of cancer in women. Science 259: 633-638, 1993Google Scholar
- 14.Clarke RB, Howell A, Potten CS, Anderson E: Dissociation between steroid receptor expression and cell proliferation in the human breast. Cancer Res 57: 4987-4991, 1997Google Scholar
- 15.Shoker BS, Jarvis C, Clarke RB, Anderson E, Hewlett J, Davies MPA, Sibson DR, Sloane JP: Estrogen receptorpositive proliferating cells in the normal and precancerous breast. Am J Pathol 155: 1811-1815, 1999Google Scholar