Comparison of immunohistochemical and biochemical measurement of steroid receptors in primary breast cancer: Evaluation of discordant findings

Tumor samples of 240 patients with primary breast cancer were biochemically and immunohistochemically investigated for estrogen receptors (ER) and, in 130 of the samples, for progesterone-receptors (PgR) in order to examine reasons for discordant findings. The biochemical (DCCA) and immunohistochemical assays (ICA) yielded positivity in 71% for ER, and in 44% for PgR. Concordant ER-DCCA and ER-ICA results were obtained in 84%; two thirds of the discordant ER-findings manifested as DCCA-neg/ICA-pos. Concordance in the case of PgR amounted to 72%, and of the discordances 60% were DCCA-neg/ICA-pos. Significant association with postmenopausal status existed only for ER positivity in ICA (p=0.01), whereas ER-DCCA, PgR-DCCA and PgR-ICA were all more or less independent of the menopausal status. The frequency of discordances was independent of menopausal status. Discordance for ER-assays increased significantly near the respective cut-off point; this was not unequivocally true for PgR-assays. The correlation of tumor types of sparse cellularity, as well as prominent stroma content (‘scirrhous carcinoma’) with increased frequency of the constellation DCCA-neg/ICA-pos was of borderline significance for PgR (p=0.06), but not for ER. The percentage of discordant ER-findings, figuring as DCCA-neg/ICA-pos, was statistically significantly increased in locally advanced breast cancer (p=0.03). Fibrocystic disease in peritumoral breast tissue had no impact on receptor-assay discordance. In any case, the models derived from theoretical thought, laboratory data and singular observations can only in part explain the discordance in steroid receptor values measured with different methods.

[1]  D. Allred,et al.  Estrogen receptor status (ER) determined by immunohistochemistry (IHC) is superior to biochemical ligand-binding (LB) assay for evaluating breast cancer patients , 1997 .

[2]  Stephen E. Jones.  Implications of the NIH Consensus Development Conference on the Treatment of Early-Stage Breast Cancer , 1991 .

[3]  H. Sears,et al.  Breast cancer without axillary metastases. Are there high‐risk biologic subpopulations? , 1982, Cancer.

[4]  G. Shaw,et al.  Molecular biology of human T-lymphotropic retroviruses. , 1985, Cancer research.

[5]  D. Allred,et al.  Immunocytochemical analysis of estrogen receptors in human breast carcinomas. Evaluation of 130 cases and review of the literature regarding concordance with biochemical assay and clinical relevance. , 1990, Archives of surgery.

[6]  E. Szabo,et al.  Immunocytochemical analysis of estrogen receptors as a predictor of prognosis in breast cancer patients: comparison with quantitative biochemical methods. , 1989, Cancer research.

[7]  William H. Hartmann,et al.  The World Health Organization Histological Typing of Breast Tumors—Second Edition , 1982 .

[8]  M. Schemper,et al.  Immunocytochemical localization of estrogen and progesterone receptor and prognosis in human primary breast cancer. , 1990, Cancer research.

[9]  M. Rogers,et al.  Estrogen receptor expression of benign breast epithelium and its association with breast cancer. , 1994, Cancer research.

[10]  S. Saez,et al.  Estradiol and progesterone receptor levels in human breast adenocarcinoma in relation to plasma estrogen and progesterone levels. , 1978, Cancer research.

[11]  J. Coindre,et al.  Production of monoclonal antibodies to human estrogen‐receptor protein (ER) using recombinant ER (RER) , 1993, International journal of cancer.

[12]  I. Christensen,et al.  Short recurrence-free survival associated with high oestrogen receptor levels in the natural history of postmenopausal, primary breast cancer. , 1993, European journal of cancer.

[13]  H. Wieand,et al.  Comparison of estrogen receptor determinations by a biochemical ligand‐binding assay and immunohistochemical staining with monoclonal antibody ER1D5 in females with lymph node positive breast carcinoma entered on two prospective clinical trials , 1996, Cancer.

[14]  B. Asselain,et al.  Prognostic value of steroid receptors after long-term follow-up of 2257 operable breast cancers. , 1996, British Journal of Cancer.

[15]  R. Cote,et al.  Strategies for improving the immunohistochemical staining of various intranuclear prognostic markers in formalin-paraffin sections: androgen receptor, estrogen receptor, progesterone receptor, p53 protein, proliferating cell nuclear antigen, and Ki-67 antigen revealed by antigen retrieval techniques , 1994, Human pathology.

[16]  S. Gebhard,et al.  Oestrogen receptor, progesterone receptor, pS2, ERD5, HSP27 and cathepsin D in invasive ductal breast carcinomas , 1993, Histopathology.

[17]  D. Barnes,et al.  Immunohistochemical determination of oestrogen receptor: comparison of different methods of assessment of staining and correlation with clinical outcome of breast cancer patients. , 1996, British Journal of Cancer.

[18]  W. McGuire,et al.  Correlations between estrogen receptor, progesterone receptor, and patient characteristics in human breast cancer. , 1984, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  S. Edge,et al.  Treatment of early-stage breast cancer. , 1999, Current problems in cancer.

[20]  G. Hortobagyi,et al.  Comparison of immunocytochemical and biochemical assays for estrogen receptor in fine needle aspirates and histologic sections from breast carcinomas , 1990, Breast Cancer Research and Treatment.

[21]  J. Durant,et al.  Evidence that estrogen‐receptor‐negative, progesterone‐receptor‐positive breast and ovarian carcinomas contain estrogen receptor , 1981, Cancer.

[22]  J. Isola,et al.  Discordant results between radioligand and immunohistochemical assays for steroid receptors in breast carcinoma. , 1990, British Journal of Cancer.

[23]  G. Leclercq,et al.  Estrogen and progesterone receptors in human breast cancer. , 1977 .

[24]  W. Schuette,et al.  Influence of cell proliferation and cell cycle phase on expression of estrogen receptor in MCF-7 breast cancer cells. , 1984, Cancer research.

[25]  M. Beato,et al.  Immunochemical characterization of wild‐type and variant glucocorticoid receptors by monoclonal antibodies. , 1984, The EMBO journal.

[26]  J. Raemaekers,et al.  Disease-free interval and estrogen receptor activity in tumor tissue of patients with primary breast cancer: analysis after long-term follow-up , 2005, Breast Cancer Research and Treatment.

[27]  H. Bloom,et al.  Histological Grading and Prognosis in Breast Cancer , 1957, British Journal of Cancer.

[28]  R. Simon,et al.  Estrogen receptor values in patients with benign breast disease , 1979, Cancer.

[29]  I. Christensen,et al.  The prognostic value of immunohistochemical estrogen receptor analysis in paraffin-embedded and frozen sections versus that of steroid-binding assays. , 1990, European journal of cancer.

[30]  F. Parl,et al.  Discrepancies of the biochemical and immunohistochemical estrogen receptor assays in breast cancer. , 1988, Human pathology.

[31]  A. Dc,et al.  Should immunohistochemical examination replace biochemical hormone receptor assays in breast cancer , 1993 .

[32]  E. Milgrom,et al.  Immunocytochemical study with monoclonal antibodies to progesterone receptor in human breast tumors. , 1987, Cancer research.

[33]  W. McGuire,et al.  Progesterone receptors and human breast cancer , 2005, Breast Cancer Research and Treatment.

[34]  E. Haus,et al.  Estrogen and progesterone receptors in human breast cancer. Correlation with histologic subtype and degree of differentiation , 1986, Cancer.

[35]  E. Milgrom,et al.  Immunocytochemical study of mammalian progesterone receptor using monoclonal antibodies. , 1985, Endocrinology.

[36]  F. Spyratos,et al.  Prognostic value of estrogen and progesterone receptors in primary infiltrating ductal breast cancer. A sequential multivariate analysis of 1262 patients. , 1989, European journal of cancer & clinical oncology.

[37]  G. Greene,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 , 1990, Cancer.

[38]  G M Clark,et al.  Steroid receptors and other prognostic factors in primary breast cancer. , 1988, Seminars in oncology.

[39]  J. Spona,et al.  A prospective analysis of immunohistochemically determined hormone receptors and nuclear features as predictors of early recurrence in primary breast cancer , 2004, Breast Cancer Research and Treatment.

[40]  R. Millis,et al.  Problems in Breast Pathology , 2006, Virchows Archiv.

[41]  R. Coombes,et al.  Characterization of estrogen receptor messenger RNA in human breast cancer. , 1987, Cancer research.

[42]  M. Henderson,et al.  Oestrogen receptor assay of breast cancer by immunocytochemistry of fine needle aspirates. , 1991, The Australian and New Zealand journal of surgery.

[43]  G. Greene,et al.  Immunochemical studies of estrogen receptors. , 1984, Journal of steroid biochemistry.

[44]  I. Christensen,et al.  Immunocytochemical detection of progesterone receptor in breast cancer with monoclonal antibody. Relation to biochemical assay, disease‐free survival, and clinical endocrine response , 1988, Cancer.

[45]  G. Greene,et al.  Monoclonal antibodies to estrophilin: probes for the study of estrogen receptors. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[46]  S. Bacus,et al.  Quantification of estrogen receptors on paraffin-embedded tumors by image analysis. , 1991, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[47]  W. Bezwoda,et al.  The value of estrogen and progesterone receptor determinations in advanced breast cancer. Estrogen receptor level but not progesterone receptor level correlates with response to tamoxifen , 1991, Cancer.

[48]  R. Coombes,et al.  Oestrogen receptor content of normal breast cells and breast carcinomas throughout the menstrual cycle , 1988, British medical journal.

[49]  J M Esteban,et al.  Biologic significance of quantitative estrogen receptor immunohistochemical assay by image analysis in breast cancer. , 1994, American journal of clinical pathology.