Bimodal Frequency Distribution of Estrogen Receptor
Bimodal Frequency Distribution of Estrogen Receptor
Immunohistochemical analysis is used routinely to determine the estrogen receptor (ER) status of breast cancers in paraffin sections. However, lack of standardization has raised concerns that weakly ER+ tumors often are classified erroneously as ER–. To determine the frequency of weakly ER+ tumors, we reviewed ER immunostains of 825 breast cancers. For each case, we estimated the proportion of ER+ tumor cells and also determined an Allred score (which results in scores of 0 or 2 through 8, based on staining intensity and proportion of positive cells). In 817 cases (99.0%), tumor cells showed complete absence of staining or staining in 70% or more of the cells. Similarly, 818 cases (99.2%) exhibited Allred scores of 0 or of 7 or 8. Thus, with the immunohistochemical method used in our laboratory, ER staining is essentially bimodal. The overwhelming majority of breast cancers are either completely ER– or unambiguously ER+, and cases with weak ER immunostaining are rare.
The use of immunohistochemical analysis to assess the estrogen receptor (ER) status of breast cancers in paraffin sections is now a routine part of pathology practice worldwide. Although ER status as determined by immunohistochemical analysis has been shown to be a prognostic factor for patients with breast cancer, the major goal of determining ER status in current clinical practice is to assess the likelihood of response to hormonal therapy. In this regard, several studies have indicated that ER by immunohistochemical analysis is not only predictive of response to endocrine therapy but also that its ability to predict such responses is superior to that of ER status as determined by ligand-binding assays.
Despite the widespread use of this procedure, the lack of standardization of methods, scoring, and threshold for ER positivity has raised concerns that a substantial minority of patients is being misclassified with regard to the ER status of their tumors when immunohistochemical analysis performed on paraffin sections is used for this purpose. There has been particular concern that weakly ER+ tumors are erroneously being categorized as ER– and that this in turn results in such patients being denied potentially beneficial antiestrogen therapy. It has been our experience that weakly ER+ tumors with the ER immunohistochemical method used in our laboratory are distinctly uncommon. To address this issue in a formal manner, we reviewed all ER immunohistochemical stains performed in our laboratory during a 2-year period. The results of this analysis indicated that in more than 99% of the cases we studied, the ER staining results were completely negative or unequivocally positive and that weakly positive cases are encountered only infrequently.
Immunohistochemical analysis is used routinely to determine the estrogen receptor (ER) status of breast cancers in paraffin sections. However, lack of standardization has raised concerns that weakly ER+ tumors often are classified erroneously as ER–. To determine the frequency of weakly ER+ tumors, we reviewed ER immunostains of 825 breast cancers. For each case, we estimated the proportion of ER+ tumor cells and also determined an Allred score (which results in scores of 0 or 2 through 8, based on staining intensity and proportion of positive cells). In 817 cases (99.0%), tumor cells showed complete absence of staining or staining in 70% or more of the cells. Similarly, 818 cases (99.2%) exhibited Allred scores of 0 or of 7 or 8. Thus, with the immunohistochemical method used in our laboratory, ER staining is essentially bimodal. The overwhelming majority of breast cancers are either completely ER– or unambiguously ER+, and cases with weak ER immunostaining are rare.
The use of immunohistochemical analysis to assess the estrogen receptor (ER) status of breast cancers in paraffin sections is now a routine part of pathology practice worldwide. Although ER status as determined by immunohistochemical analysis has been shown to be a prognostic factor for patients with breast cancer, the major goal of determining ER status in current clinical practice is to assess the likelihood of response to hormonal therapy. In this regard, several studies have indicated that ER by immunohistochemical analysis is not only predictive of response to endocrine therapy but also that its ability to predict such responses is superior to that of ER status as determined by ligand-binding assays.
Despite the widespread use of this procedure, the lack of standardization of methods, scoring, and threshold for ER positivity has raised concerns that a substantial minority of patients is being misclassified with regard to the ER status of their tumors when immunohistochemical analysis performed on paraffin sections is used for this purpose. There has been particular concern that weakly ER+ tumors are erroneously being categorized as ER– and that this in turn results in such patients being denied potentially beneficial antiestrogen therapy. It has been our experience that weakly ER+ tumors with the ER immunohistochemical method used in our laboratory are distinctly uncommon. To address this issue in a formal manner, we reviewed all ER immunohistochemical stains performed in our laboratory during a 2-year period. The results of this analysis indicated that in more than 99% of the cases we studied, the ER staining results were completely negative or unequivocally positive and that weakly positive cases are encountered only infrequently.