Immunohistologic localization of estrogen receptors in breast cancer with monoclonal antibodies. Correlation with biochemistry and clinical endocrine response

Abstract

Breast cancer specimens from 114 patients were assayed for the presence of estrogen receptors (ER) utilizing highly specific, monoclonal antiestrophilin antibodies and the peroxidase‐antiperoxidase technique. Results were compared with conventional ER determinations by the dextran‐coated charcoal method (DCC) and were in agreement as to positivity and negativity in 86%. Semiquantifled immunocytologic assay results were in accord with the level of ER as measured by DCC in 66%. The tumors studied included 43 from patients with Stage IV disease where clinical response to hormonal manipulation was known. In the latter group, the immunohistologic method had a sensitivity similar to that of DCC but showed a superior positive predictive value and a significantly better specificity. These results indicate that this new method is a valuable laboratory tool, enabling prediction of hormone responsiveness in advanced mammary carcinoma and capable of performance at the community hospital level.

Immunocytochemical assay for oestrogen receptor in fine needle aspirates of breast cancer by video image analysis

“…If one wishes to measure the IOD of individual nuclei in frozen sections, extensive programming is required to account for the fact that the majority of cancer nuclei are not sectioned through the greatest diameter of the cell -even if they all could be assumed to be of the same size and shape. As observed by Sklarew & Pertschuk (1987), an important consideration in densitometry of sectioned material is the effect of nuclear volume distribution on the observed receptor concentration (mean optical density). Using nuclear volumes derived from projected nuclear areas, these workers determined that the presence of well-separated concentration peaks could not be ascribed to differences in ER content, but were dependent on variations in nuclear volume.…”

“…Sensitivity equalled 89% and specificity equalled 100%. This association between ER positivity of breast cancers as analysed by DCC and ERICA (Table III) Pertschuk et al (1985) (80% versus 58%).…”

“…The majority of research groups performing ER immunocytochemistry on frozen sections or fine needle aspirate have employed a histological scoring index based on a combination of visual analyses of the intensity of immunostaining and proportion of immunostained nuclei (King et al, 1985;Pertschuk et al, 1985;Azavedo et al, 1986;Flowers et al, 1986;Jonat et al, 1986). This approach can lead to a high degree of subjectivity in the assessment of staining intensity and hence the proportion of stained nuclei, and this is difficult to control.…”

“…The intra-and inter-observer variation in assessments can be minimised by the use of a computerised system of image analysis. To date there have been few published reports of video image analysis applied to the estimation of ER heterogeneity in breast cancer nuclei (Charpin et al, 1986;Sklarew & Pertschuk, 1987;Franklin et al, 1987). With these systems, background staining in control populations of cells due to endogenous peroxidase and non-specific antibody binding can be readily quantitated by the computer system, thereby improving the reliability of the measurements.…”

Histochemical studies of human breast cancer using a monoclonal antibody against an oestrogen receptor-related antigen

“…For the purpose of immunohistochemistry, antibodies of both polyclonal (Tamura et al, 1984;Lope-Pihie et al, 1985) and monoclonal type (Greene et al, 1980;Coffer & King, 1981) have been generated and amongst these, one in particular (Greene et al, 1980) has been demonstrated to reflect accurately oestrogen receptor (R) status, in several different centres Pertschuk et al, 1985;Hawkins et al, 1986).…”