Abstract
A retrospective study comparing the estrogen receptor (ER) a subtype and progesterone receptor (PR) profile of breast carcinomas amongst 1625 cases over 2.5 years was carried out. Strictly speaking it is generally believed that breast carcinomas can biochemically express PR only if they are ER-positive. However, a few ERα-PR+ cases do exist paradoxically. This class of tumors was the focus of our study in which we looked at the possible reasons for such an immunophenotype and compared it with a group of ERα+PR+ breast carcinomas. An internationally recognized immunohistochemical method employing monoclonal antibodies against estrogen and progesterone receptors was used. Correlations with established risk factors i.e. menopausal status, grade, tumor size and lymph node status were analyzed for our study group (ERα-PR+) and compared with a control (ERα+PR+). Out of the total 1625 cases, 29.91% (486) were ERα+PR+, 5.11% (83) were ERα+PR-, 56.86% (924) were ERα-PR- and 8.12% (132) were ERα-PR+. Patients’ age was significantly lower in the ERα-PR+ group (P=0.002). Statistical analysis of the grading between the two study groups revealed no significant difference (P=0.091), although the ERα-PR+ group contained significantly more poorly differentiated tumors than the ERα+PR+ one (P=0.032). Tumor size was also significantly larger in the ERa-PR+ than in the ERα+PR+ group (P=0.046). The frequency of lymph node metastases was independent of receptor profile. In conclusion, our study group does exhibit characteristics which are suggestive of a distinct breast cancer phenotype (ERα-PR+) with a different etiology and prognosis.
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References
Ballare C, Bravo, AI, Sorin I, et al: The expression of progesterone receptors coincides with an arrest of DNA synthesis in human breast cancer. Cancer 67: 1352–1358, 1991
Berger U, McLelland RA, Wilson P, et al: Immunohistochemical determination of estrogen receptor, progesterone receptor and 1, 25-dihydroxvitamin D3 receptor in breast cancer and relationship to prognosis. Cancer Res 51: 239–244, 1991
Berkenstam A, Glaumann H, Martin M, et al: Hormonal regulation of estrogen receptor messenger ribonucleic acid in T47DCO and MCF-7 breast cancer cells. Mol Endocrinol 3: 22–28, 1989
Bloom HJG, Richardson WW: Histological grading and prognosis in breast cancer. Br J Cancer 11:359–377, 1957
deSombre, ER: Steroid receptors in breast cancer. In: The Breast. (Eds: McDivitt RW, Oberman HA, Ozello L and Kaufman N), Williams and Wilkins, Baltimore, 1984, pp149–174
Edery M, Goussard J, Dehennin L, et al: Endogenous oestradiol-17β concentration in breast tumors determined by mass fragmentography and by radioimmunoassay: relationship to receptor content. Eur J Cancer 17: 115–120, 1981
Fishman J, Nisselbaum JS, Menendez-Botet CJ, Schwartz MK: Estrogen and estradiol content in human breast tumors: relationship to estradiol receptors. J Steroid Biochem 8: 893–896, 1977
Greene GL, Press MF: Steroid receptor structure (including monoclonal antibodies and new methods of determination): structure and dynamics of the estrogen receptor. J Steroid Biochem 24: 1–7, 1986
Greene GM, Fitch FW, Jensen EV: Monoclonal antibodies to trophilin: probes for the study of estrogen receptors. Proc Natl Acad Sci USA 77: 157–161, 1980
Horwitz KB, McGuire WL: Estrogen control of progesterone receptor in human breast cancer. Correlation with nuclear processing of estrogen receptor. J Biol Chem 253: 2223–2228, 1978
Horwitz KB: Cellular heterogeneity and mutant oestrogen receptors in hormone resistant breast cancer. Cancer Surv 14: 41–54, 1992
Howat JMT, Harris M, Swindell R, Barnes DM: The effect of oestrogen and progesterone receptors on recurrence and survival in patients with carcinoma of the breast. Br J Cancer 51: 263–270, 1985
Kiang DT, Kollander R: Breast cancers negative for estrogen receptor but positive for progesterone receptor, a true entity? J Clin Oncol 5: 662–666, 1987
Leclercq G, Heuson JC, Deboel MC, et al: Estrogen and progesterone receptors in human breast cancer. In: Progesterone Receptors in Normal and Neoplastic Tissues. (Eds: McGuire WL, Raynaud J-P, Baulieu E-E), Raven, New York, 1977, pp 141–153
Leygue E, Dotzlaw H, Watson PH, Murphy LC: Altered estrogen receptor alpha and beta messenger RNA expression during human breast tumorigenesis. Cancer Res 58: 3197–3201, 1998
McGuire WL: Hormone receptors. Their role in predicting prognosis and response to endocrine therapy. Semin Oncol 5: 428–433, 1979
McGuire WL, Horwitz KB, Pearson DH, Segaloff A: Current status of estrogen and progesterone receptors in breast cancer. Cancer 39: 2934–2947, 1977
McGuire WL: Steroid receptors in human breast cancer. Cancer Res 38: 4289–4291, 1978
Nuclear Receptors Nomenclature Committee: A unified nomenclature system for the nuclear receptor superfamily. Cell 97:161–163, 1999
Osborne CK, Yochmowitz MG, Knight WA, McGuire WL: The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer 46: 2884–2888, 1980
Osborne CK: Receptors. In: Breast Diseases. (Eds: Harris JR, Hellman S, Henderson IC, Kinne DW), 2nd ed, JB Lippincott Co, Philadelphia, PA, 1991, pp 301–325
Panko WB, MacLeod RM: Uncharged nuclear receptors for estrogen in breast cancers. Cancer Res 38: 1948–1951, 1978
Perrot-Applanat M, Logeat F, Croyer-Picard MT, Milgrom E: Immunocytochemical study of mammalian progesterone receptor using monoclonal antibodies. Endocrinology 116: 147–1483, 1985
Pertschuk LP. Kim DS, Kamran Nayer MA, et al: Immunocytochemical estrogen and progestin receptor assays in breast cancer with monoclonal antibodies. Cancer 66: 1663–1670, 1990
Pichon MF, Milgrom E: Oestrogen receptor negative-progesterone receptor positive phenotype in 1,211 breast tumors. Br J Cancer 65: 895–897, 1992
Reiner A, Neumeister B, Spona J, et al: Immunocytochemical localization of estrogen and progestin and prognosis in human primary breast cancer. Cancer Res 50: 7057–7061, 1990
Saez S, Martin PM, Chouvet CD: Estradiol and progesterone receptors in human breast adenocarcinoma in relation to plasma estrogen and progesterone levels. Cancer Res 38: 3468–3473, 1978
Sarrif AM, Durant JR: Evidence that estrogen-receptor-negative progesterone-receptor-positive breast and ovarian carcinomas contain estrogen receptor. Cancer 48: 1215–1220, 1982
Savouret J-F, Fridlanski F, Atger M, et al: Origin of the high constitutive level of progesterone receptor in T47-D breast cancer cells. Mol Cell Endocrinol 75: 157–162, 1991
Shaaban AM, O’Neill PA, Davies MP, et al: Declining estrogen receptor beta expression defines malignant progression of human breast neoplasia. Am J Surg Pathol 27: 1502–1512, 2003
Shapiro CM, Schiffeling D, Bitran JD, et al: Prognostic value of estrogen receptor value in pathologic stage 1 and 2 adenocarcinoma of the breast. J Surg Oncol 19: 119–121, 1982
Shigehira S, Makiko H, Masakazu T: Clinical significance of estrogen receptor β in breast cancer. Cancer Chemother Pharmacol 56: s21-s26, 2005
Speirs V, Skliris GP, Burdall SE, Carder PJ: Distinct expression patterns of ER alpha and ER beta in normal human mammary gland. J Clin Pathol 55: 371–374, 2002
Thorpe SM: Immunological quantitation of nuclear receptors in human breast cancers: relation to cytosolic estrogen and progesterone receptors. Cancer Res 47: 1830–1835, 1987
Thorsen T: Occupied and unoccupied oestradiol receptor in human breast tumor cytosol. J Steroid Biochem. 24: 1–7, 1986
Toft DO, O’Malley BW Target tissue receptors for progesterone: The influence of estrogen treatment. Endocrinology 90: 1041–1045, 1972
Vihko R, Janne O, Kontula K, Syrjala P: Female sex steroid receptor status in primary and metastatic breast carcinoma and its relationship to serum steroid and peptide hormone levels. Int J Cancer 26: 13–21, 1980
Watson CS, Medina D, Clark JH: Characterization and estrogen stimulation of cytoplasmic progesterone receptor in the ovarian-dependent MXT-3590 mammary tumour line. Cancer Res 39: 4098–4104, 1979
Zava DT, Chamness GC, Horwitz KB, McGuire WL: Biologically active estrogen receptor in the absence of estrogen. Science 196: 663–664, 1977
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Kiani, J., Khan, A., Khawar, H. et al. Estrogen receptor α-negative and progesterone receptor-positive breast cancer: Lab error or real entity?. Pathol. Oncol. Res. 12, 223–227 (2006). https://doi.org/10.1007/BF02893416
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DOI: https://doi.org/10.1007/BF02893416