Estrogen Receptor In Breast Carcinoma Research Articles

Estrogen Receptor Is Expressed in Uveal Melanoma: A Potential Target for Therapy

Background: Metastatic uveal melanoma (UM) has no effective treatment. To date, no publications have reported immunohistochemical evidence of estrogen receptors (ERs) in UM; however, changes in pathologic reporting for ER in breast carcinoma prompted a re-examination of ER in UM, as it could represent a potential therapeutic target. Objective: To determine if UM tumors express ER by immunohistochemistry (IHC) using current methodology for breast cancer and to evaluate ER gene expression using a publicly available UM database. Methods: A retrospective IHC analysis with clinical correlation was performed on 2 cohorts: 57 cases from the Cleveland Clinic (CC) and 50 from the Ohio State University Wexner Medical Center (OSUWMC). Analysis of The Cancer Genome Atlas Project (TCGA) UM Dataset of 80 patients was also performed. Results: Presence of ER was detected by IHC in 20 of 34 (59%) analyzable cases in the CC cohort. Of the 50 patients in the OSU cohort, 52 specimens from 47 patients were sufficient for analysis. Of these 47 cases, 29 (62%) had tumor that was ER positive in ≥1% nuclei. In the second cohort, positivity was classified as positive (≥10% nuclei, 34% cases) or low positive (1–9% nuclei, 28% cases). In 5 patients, there were paired samples, that is, primary tumor and subsequent recurrence or metastasis, with concordance for ER in 4 of 5 cases. In the TCGA database, elevated ESR1 and ESR2 gene expression was identified in a subset of UM tumors with poor genetic prognostic features. Conclusions and Relevance: Potentially actionable ER expression is present in greater than half of UM cases by IHC. Gene expression of ESR1 and ESR2 was elevated in a subset of UM tumors with poor prognostic features. These data provide a rationale to evaluate ER as a potential target for therapy in UM.

AKT signaling pathway in invasive ductal carcinoma of the breast: correlation with Erα, ERβ and HER-2 expression

Estradiol exerts most of its effects by direct binding to the estrogen receptor in breast carcinoma, ERβ expression is a useful biomarker for breast cancer in a manner that is independent of ERa expression. However, studies evaluating ERβ expression with certain tumor variables, such as tumor grade and disease-free survival, had produced conflicting results. The Akt signaling pathway currently attracts considerable attention as a new target for effective therapeutic strategies. The current study attempted to compare the relative associations of variables including ERa, ERβ, HER-2/neu and AKT staining with the presence of metastases or survival. Immunohistochemical staining was employed to determine the expression of ERa, ERβ, pAkt and HER-2/neu in 110 cases of primary breast carcinoma. Positive ERa, ERβ, pAkt and HER-2/neu expressions were respectively observed in 46.4% (51/110), 59.1% (65/110), 40.9% (45/110) and 31.8% (35/110) of the tumors. pAkt was significantly associated with HER-2/neu overexpression (P <0.005) and axillary lymph node metastasis (P <0.05). However, there was no significant relationship between pAkt and ERa, ERβ, p53 (P >0.05) expressions. Survival analysis showed that pAkt positivity was associated with poor disease-free survival of the patients. The current study suggested that activity of the Akt signaling pathway may indicate a poor prognosis in patients with breast carcinoma. The results implied that estrogen can activate the PI3K-Akt pathway through ERa and ERβ-independent mechanisms in breast cancer.

AKT Signaling Pathway in Invasive Ductal Carcinoma of the Breast: Correlation with ERα, ERβ and HER-2 Expression

Estradiol exerts most of its effects by direct binding to the estrogen receptor in breast carcinoma, ERβ expression is a useful biomarker for breast cancer in a manner that is independent of ERa expression. However, studies evaluating ERβ expression with certain tumor variables, such as tumor grade and disease-free survival, had produced conflicting results. The Akt signaling pathway currently attracts considerable attention as a new target for effective therapeutic strategies. The current study attempted to compare the relative associations of variables including ERa, ERβ, HER-2/neu and AKT staining with the presence of metastases or survival. Immunohistochemical staining was employed to determine the expression of ERa, ERβ, pAkt and HER-2/neu in 110 cases of primary breast carcinoma. Positive ERa, ERβ, pAkt and HER-2/neu expressions were respectively observed in 46.4% (51/110), 59.1% (65/110), 40.9% (45/110) and 31.8% (35/110) of the tumors. pAkt was significantly associated with HER-2/neu overexpression (P <0.005) and axillary lymph node metastasis (P <0.05). However, there was no significant relationship between pAkt and ERa, ERβ, p53 (P >0.05) expressions. Survival analysis showed that pAkt positivity was associated with poor disease-free survival of the patients. The current study suggested that activity of the Akt signaling pathway may indicate a poor prognosis in patients with breast carcinoma. The results implied that estrogen can activate the PI3K-Akt pathway through ERa and ERβ-independent mechanisms in breast cancer.

The prognostic significance of a combined determination of cathepsin D and estrogen receptors in breast carcinomas with positive axillary lymph nodes

OBJECTIVE The aim of this study was to investigate the correlation between cathepsin D (Cath-D) and estrogen receptor (ER)expression in breast cancer tissue and to explore the prognostic significance of their combined determination in breast carcinoma patients with positive axillary lymph nodes.

Automated subcellular localization and quantification of protein expression in tissue microarrays.

The recent development of tissue microarrays-composed of hundreds of tissue sections from different tumors arrayed on a single glass slide-facilitates rapid evaluation of large-scale outcome studies. Realization of this potential depends on the ability to rapidly and precisely quantify the protein expression within each tissue spot. We have developed a set of algorithms that allow the rapid, automated, continuous and quantitative analysis of tissue microarrays, including the separation of tumor from stromal elements and the sub-cellular localization of signals. Validation studies using estrogen receptor in breast carcinoma show that automated analysis matches or exceeds the results of conventional pathologist-based scoring. Automated analysis and sub-cellular localization of beta-catenin in colon cancer identifies two novel, prognostically significant tumor subsets, not detected by traditional pathologist-based scoring. Development of automated analysis technology empowers tissue microarrays for use in discovery-type experiments (more typical of cDNA microarrays), with the added advantage of inclusion of long-term demographic and patient outcome information.

Imprint Immunocytochemistry of Estrogen Receptors in Breast Carcinoma

To clarify the accuracy of immunocytochemical detection of estrogen receptors (ER) in breast carcinomas using cytological materials, imprint specimens from tumor tissue were compared with frozen tissue sections and tumors analyzed by the dextran coated charcoal (DCC) method and enzyme immunoassay (EIA). Out of 50 cases examined by imprint immunocytochemistry, there were 39 ER positive cases (78.0% positivity). The positivity in the imprint materials agreed with that of the DCC in 36 out of 40 cases (85.0%), with 100% sensitivity and 60.0% specificity. The two methods statistically correlated with each other in their positivity and grade (p less than 0.001). The positivity and grades of imprint and frozen immunocytochemistry as well as those of imprint immunocytochemistry and the EIA agreed almost perfectly with each other. As a result of the present study, we concluded that immunocytochemical detection of ER is indeed reliable, as accurate as other procedures. We recommend that aspiration biopsy cytology (ABC) be used for morphological examination and ER immunocytochemistry when adequate materials are available and that imprint materials be used when ABC materials are inadequate and fresh tissue is available at the time of surgery.

Image cytometry of estrogen receptors in breast carcinomas

A significant level of estrogen receptors (ER) in breast cancer cells is an indication of tumor differentiation and suggests that a homeostatic control of cell growth may persist in these cancers. In medical practice, the Dextran-coated charcoal assays (DCCA) are still the most frequently used test to characterize patients having ER-positive malignant breast tumors and for whom hormonal therapy is justified. Nevertheless, this routine biochemical technique is not satisfactory because it is a broad method unsuitable for revealing receptor tissue heterogeneity. However, immunocytochemical labeling, such as the ER-ICA method, which involves a monoclonal antibody linked to peroxidase, is a specific reaction for this purpose but which until now was not quantitative. The present study uses an original cell preparation technique combining the PAP reaction with toluidine blue counterstain for image analysis on the SAMBA system. Special software has been developed for the quantitative analysis of immunocytochemistry in cancers. Results obtained showed a high correlation between the DCCA values and the score derived from the mean ER concentration per positive tumor cell and the labeling index. In addition, intracell and intratumor heterogeneity can be displayed according to several parameters and were shown to vary according to tumor and to antiestrogen (Tamoxifen) presurgical therapy.

Histochemical detection of oestrogen receptors in breast carcinoma: a successful technique.

Histochemical detection of oestrogen receptors in breast carcinoma: a successful technique.

Comparison between a biochemical and a histochemical method for the detection of oestrogen receptor in breast carcinoma.

A histochemical method for the detection of oestrogen receptors in breast carcinoma is used to examine 48 cases of primary breast cancer and a comparison made with the standard biochemical method. Positive correlation between the two methods is shown in 85.4% of cases, a result which is statistically significant (p<0.02). Some points of advantage and disadvantage in both methods are discussed. In particular, the future role of histochemical methods in general, and of the labelled-ligand method of Lee, specifically, is considered. Although no definite clinical correlation between the histochemical method and patient management has yet been described, it is felt that the direct visualisation of oestrogen binding sites in breast cancer is a useful adjunct to the standard biochemical technique.

PAP immunoperoxidase method demonstrating endogenous estrogen in breast carcinomas.

A PAP immunoperoxidase method for demonstrating estrogen receptors in breast carcinomas is introduced. Whereas other methods pretreat the specimen with exogenous estrogen in high (unphysiologic) doses, this method demonstrates endogenous estrogen without such pretreatment. Experiments showed endogenous estrogen remaining in the formalin-fixed, paraffin-embedded breast tumors in sufficient amounts to be detected by the PAP method. The method can discriminate hormone responsive cells from hormone secreting cells because most responsive cells demonstrate both the cytoplasmic and nuclear stain and most secreting cells only the cytoplasmic stain. The method was applied to 277 human breast carcinomas, of which 197 (71.1%) were positive and 80 (28.9%) negative. These figures were comparable to those obtained by the biochemical methods. This PAP method may serve as an alternative to the biochemical assays of estrogen receptors.