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The presence of sexual steroid receptor proteins in thyroid tissue has been previously demonstrated by biochemical means. The aim of this study was to determine the estrogen (ER) and progesterone (PR) receptors in malignant (12 papillary and 1 follicular carcinoma) and nonmalignant (19 multinodular goiters, 1 Graves' disease, 1 Hashimoto's thyroiditis) thyroid diseases using immunocytochemical assay employing monoclonal anti-ER and anti-PR antibodies and the peroxidase-antiperoxidase technique. Positive results were obtained in 24/34 (70%) for ER (ER-ICA+) and 22/34 (64%) for PR (PR-ICA+). To evaluate the possible interference of thyroperoxidase in the immunostaining, in consecutive sections of a positive specimen, primary antibody or primary antibody plus bridging antibody or PAP complex was omitted. Using these modified procedures, staining distribution was similar to that obtained by the standard procedure: in contrast, no staining was found in the positive control, i.e. a breast cancer specimen. The inhibition of the endogenous peroxidase caused a loss of staining in both the standard and modified procedures on thyroid specimens; no staining modification was obtained in the positive control. These results suggest that the staining observed in thyroid tissue is not specific and related to the activity of thyroperoxidase on chromogen solution. The complete loss of staining after peroxidase inhibition appears to be in contrast with the results obtained by biochemical method, and different antigenicity of thyroid receptors in comparison with breast receptors may explain this discrepancy.

The production of monoclonal antibodies against estrogen receptor (ER) and progesterone receptor (PR) has permitted the development of the enzyme immunoassay (EIA) and immunocytochemical assay (ICA) for steroid receptor determination. The results obtained with these two techniques, using the same monoclonal antibodies, were compared in a large series of breast carcinomas (187 for ER and 100 for PR). The correlation between these methods was significant for ER (rs = 0.54) and PR (rs = 0.55) (P less than 0.001) but was lost when the receptor concentrations determined by EIA were less than or equal to 15 and less than or equal to 30 fmol/mg protein for ER and PR, respectively. When these values are considered as cutoffs, the concordance between the two methods was 84.5% for ER and 73% for PR. An analysis of discordant results revealed that low epithelial cellularity generally was present in ICA-positive, EIA-negative specimens, whereas only focal positivity with ICA, or positivity of only normal peripheral mammary ducts and lobules, frequently was found in ICA-negative, EIA-positive tumors. In conclusion, there is good correlation between the results obtained by EIA and ICA methods for detection of ER and PR. The authors suggest that biochemical and histochemical methods for steroid receptors could be considered complementary and used together for the analysis of breast cancer.

The correlation of the most important prognostic indicators was evaluated in 75 breast cancer cases. Estrogen-progesterone receptors and proliferating activity were analyzed by immunocytochemical methods (ER-ICA, PR-ICA, Ki-67). Both steroid receptors were inversely correlated with the proliferating activity (ER-ICA vs Ki-67, p less than 0.003; PR-ICA vs. Ki-67, p less than 0.0001). No correlation was found between steroid receptors or cell kinetics and tumor size or lymph node status. These findings confirm the relevance of biochemical and kinetic parameters as independent markers in breast cancer and suggest a routine use of the simple immunocytochemical methods in assessing the biological behavior of tumors.

We studied the relationship between steroid receptors (SR) and various stromal parameters in 100 breast cancers. Each specimen was submitted to SR determination by the dextran-coated charcoal assay and to histologic examination. No relationship was found between the presence of SR and necrosis or fibroblastic cell content. There was an inverse correlation between SR positivity and the extent of lymphocyte infiltration (p less than 0.05). ER + PR + status was strongly correlated with marked productive fibrosis (PF) (p less than 0.005). When SR were separately assayed, only the presence of PR was correlated with PF (p less than 0.005); similar results were obtained for PR levels (p less than 0.01). PF was also associated with a higher nuclear grade (p less than 0.001). In conclusion, in this study a strong correlation between PR positivity or concentration and extent of PF was demonstrated in breast cancer. Since PR synthesis is an expression of an intact regulatory pathway, our data suggest that stromal production in breast cancer is related to the degree of differentiation of malignant epithelial cells.

The presence of progesterone receptor (PR), productive fibrosis (PF), axillary nodal status and tumor size are important prognostic variables in breast cancer. In this study we have analyzed the relationship between these four parameters in 78 ductal infiltrating carcinomas of the breast. No relationship was found between PF and the presence of lymph node metastatic disease: however, in the tumors with positive nodes, a limited metastatic diffusion (1-3 lymph nodes) was significantly associated with PF (p less than 0.05). Our study failed to demonstrate any relation between estrogen receptor (ER) and both presence and extension of nodal involvement; in contrast, the tumors with limited metastatic diffusion (1-3 lymph nodes) had a significantly higher prevalence of PR positivity (p less than 0.05). Furthermore, PF was strongly associated with PR (p less than 0.001) and less well with ER (p less than 0.05). The simultaneous presence of PR and marked PF was strongly correlated with limited metastatic involvement of the axilla (p less than 0.007). Tumor size was correlated with the number of positive nodes (p less than 0.001), but not with PR or PF. The results demonstrate that PR status, PF and tumor size are related to limited metastatic diffusion of the axilla: furthermore PF and PR have been shown to be strongly related and we have demonstrated that, at least in ductal infiltrating carcinoma, the simultaneous presence of them identifies a subset of tumors with low metastatic capacity independently of tumor size.