Lysophosphatidic receptor, LPA3, is positively and negatively regulated by progesterone and estrogen in the mouse uterus
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Progesterone receptor
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Summary Despite the controversies, estrogen receptor–negative/progesterone receptor–positive (ER−/ PR+) breast cancers have a reported incidence of 1% to 4%. These tumors are less well defined, and it is unclear whether ER−/PR+ represents a distinct subtype. Thus, we analyzed 5374 consecutive breast cancers to characterize the clinicopathological features of this underrecognized subset of tumors. The ER−/PR+ tumors, constituting 2.3% of the total, were mostly high grade and significantly seen in younger patients and African American women when compared with the ER+/PR+ and ER+/PR− groups, but similar to that of ER−/PR− phenotype (P b .0001). A significantly prolonged relapse-free survival (RFS) was associated with the ER+/PR+ subtype when compared with the ER+/PR− (P = .0002) or ER−/PR+ (P = .0004) tumors, whereas all 3 groups showed a superior outcome to that of the ER−/PR− phenotype. In the subset of patients receiving endocrine therapy, those with ER+/PR+ tumors had a significantly prolonged RFS (P = .001) and disease-specific survival (P = .005) when compared with the group with an ER+/PR− phenotype, but did not significantly differ from those with ER−/PR+ tumors. No significant survival advantage was found between the ER+/PR− and ER−/PR+ tumors in any group of patients analyzed. Furthermore, a higher PR expression was associated with a favorable RFS and disease-specific survival in the patients with ER−/PR+ tumors. Therefore, the ER−/PR+ tumors demonstrate a similar, if not higher than, response rate to endocrine therapy when compared with the ER+/PR− tumors and thus are important to identify. Routine PR testing remains necessary in assisting clinical decision making in the pursuit of precision medicine.
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Objective To investigate the expressions of estrogen receptor (ER) and progesterone receptor (PR) in different tumor tissues of invasive ductal carcinoma(IDC) of the breast. Methods A total of 32 cases of IDC samples were collected. ER and PR expressions in 4 different sites of every sample were measured by immunohistochemical(IHC) assays. Results Overall, a high concordance in both estrogen receptor and progesterone receptor expressions are observed between different tumor tissue sites. The best Kappa values were 0.789 and 0.810 for ER and PR expression respectively. The worst Kappa values were 0. 563 and 0.672,respectively. Conclusion ER and PR expression is not significantly different in different tumor tissues of the same IDC sample. Repeated testing in different tumor tissue sites has little contributions in clinical settings.
Key words:
Breast neoplasms; Estrogen receptor; Progesterone receptor
Progesterone receptor
Concordance
Breast carcinoma
Estrogen receptor beta
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Expression and significance of estrogen receptor,progesterone receptor in non-small cell lung cancer
Objective To investigate the correspondence between the expression of estrogen receptor(ER),progesterone receptor(PR) in non-small lung cancer.Methods The immunohistochemical way S-P was employed to estimate the ER and PR in non-small lung cancer.Results The positive rates of ER and PR were 45.2% and 40.4%.The expression rates of ER and PR in adeno-carcinoma were apparently higher than that in other types of lung cancer tissues (P 0.01).In lung cancer the expressions of ER and PR were not related to the sex,age,clinical stage,degree of differentiation of tumor cells(P 0.05).There was no apparent difference in statistics of the non-tumor survival rate between the positive and negative ER and PR patients with in one,three postoperative years(P 0.05).Conclusion ER and PR are present in lung cancer,they can be an index as a steroid-aided therapy with a good prospect.
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The interobserver reproducibility in the immunocyto-chemical assessment of estrogen- and progesterone receptor status was investigated in a series of 102 cases of primary breast carcinomas. Immunostaining was performed on 4 microns cryostat sections using estrogen- and progesterone immunocytochemical assays (ER-ICA and PR-ICA) with methylgreen counterstaining. The slides were evaluated independently by two observers. The proportion and staining intensity of ER- or PR-positive tumor cells in areas of invasive tumor growth was subjectively assessed based on the examination of the entire slide. Scoring was performed according to the proposals of Remmele and Reiner. Additionally, the cytosol estrogen- and progesterone receptor content was determined by a standard dextran-coated charcoal (DCC-) assay. Observer 1 interpreted 60 (59%) of the ER-stained specimens and 50 (49%) of the PR-stained specimens as receptor-positive; for observer 2 the respective values were 59 (58%) for ER-stained specimens and 51 (50%) for PR-stained specimens. Positive biochemical receptor status was found in 68 cases with the ER-DCC (67%) and in 47 with the PR-DCC (46%). The interobserver agreement between the two observers on the immunocytochemical receptor status was 89% for the estrogen receptor and 93% for the progesterone receptor 8.8% of the specimens were interpreted differently. Using the Remmele score, the concordance within the group of cases, which had been interpreted as receptor-positive by both observers, was 54% for the estrogen receptor and 57% for the progesterone receptor. The Reiner score showed concordant scorings of 72% for the estrogen receptor and 79% for the progesterone receptor. The present study indicates that complete agreement between scorings of different observers may not be expected, mainly due to differences in the interpretation of the specificity of staining and of the histological structures after immunostaining. The concordance of positive results using the three-graded Reiner score is comparable to that of the three-graded Bloom and Richardson grading system of breast cancer and reflects the limitation of subjective evaluation of morphology in general.
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Objective:To analyze the expressions of estrogen receptor(ER),progesterone receptor(PR) and human epithelial receptor-2(CerbB2) in elderly patients with breast cancer,and to investigate its clinical significance.Methods:One hundred and twenty-five female breast cancer patients aged 65years and older were enrolled in the study.Clinical data of all the patients were retrospectively reviewed.Expressions of ER,PR and CerbB2 were detected by immunohistochemistry.Correlation between expressions of ER,PR and CerbB2 and tumor size,histological grade,tumor location,lymph node metastasis were statistically analyzed.Results:The positive expressions of ER,PR and CerbB2 were 84(67.2%),83(66.4%) and 25(20.0%),respectively.The expressions of ER and PR were correlated with histological grade,while CerbB2 expression was correlated with histological grade,tumor size and lymph node metastasis,respectively(both P 0.01).Three and five years overall survivals of elder patients were 74.9%and 62.0%;the mean overall survival was 6.9 years.Conclusions:The increased expressions of ER,PR and decreased expression of CerbB2 in female breast cancer patients reflected the pathobiological features of the cancer,which would be helpful for the treatment and surgical operation of breast neoplasms.
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The estrogen receptor-related antigen (ER-D5) is a serine phosphoprotein associated with the estrogen receptor that is present only in estrogen receptor- (ER) positive tissues and has no relation with progesterone receptor (PR). This study was performed to evaluate whether immunostaining of these proteins correlated with the proliferative potential of meningiomas as evaluated by clinicopathologic features.Immunohistochemical staining of ER-D5, ER, and PR were performed on paraffin embedded sections of meningiomas from 34 patients.Twenty two (64.7%) of the 34 meningiomas tested were positive for ER-D5 with exclusively cytoplasmic immunostaining. All of the cases were positive for PR but not for ER. Progesterone receptors in meningiomas were cytoplasmic and/or nuclear. The correlation of ER-D5 reactivity with histologic subtypes showed positivity rates for meningotheliomatous meningiomas of 71.4%, fibroblastic 41.7%, transitional 80%, anaplastic 100% and hemangiopericytic 100%. ER-D5 positivity rates in primary and recurrent meningiomas were 59.3% and 85.7%, respectively. Normal arachnoid tissue was positive for PR but negative for ER-D5 and ER. Patient age and sex has no significant influence on the positivity rate of meningiomas. The mean number of AgNORs in ER-D5-positive and -negative meningiomas had no statistical significance.This study suggests that ER-D5 has some role in the growth of the meningioma and that the expression of ER-D5 in human meningioma is independent of ER as it is in breast cancer. The localization of PR in the meningioma cells indicate that at least some of these cells are functionally active.
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The aim of this work was to analyze methylation of the promoter sites of the ESR1 and PGR genes and to determine correlations with immunohistochemical expression of estrogen and progesterone receptors in ductal and lobular breast cancers. An observational, descriptive, molecular study was conducted on 20 ductal and 20 lobular breast cancer samples with immunohistochemical determination of estrogen and progesterone receptor expression. The methylation analysis of ESR1 and PGR promoter sites was carried-out by methylation-specific PCR. For correlation analysis, Kendall's tau coefficient was determined. Positive correlations were found between estrogen and progesterone receptors, estrogen receptor and unmethylated progesterone receptor, progesterone receptor, and unmethylated progesterone receptor. Negative correlations were found between estrogen receptor and methylated progesterone receptor, progesterone receptor and methylated progesterone receptor, methylated and unmethylated estrogen receptor, and methylated and unmethylated progesterone receptor. The results suggest that methylation of promoter sites of ESR1 and PGR is a relatively uncommon event in ductal and lobular breast cancer, and also suggest that the determination of epigenetic states of ESR1 and PGR could represent an alternative or complement to the histopathological expression analysis.
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In a series of 256 mammary carcinomas, 22 (8.5%) were positive for progesterone receptors (PR) and negative for estrogen receptors (ER). These cases seem to belong to a distinctive group with a biologic behavior not well understood. In order to contribute to a better understanding of such tumors, their association with different pathologic and immunohistochemical factors were compared with those of the rest of the tumors of the series. The results were that favorable factors such as smaller size, negative axillary lymph nodes and low histologic and nuclear grades were decreasingly associated with tumors that were ER+ PR+; ER+ PR-; ER- PR+; and ER- PR-. In relation to immunohistochemical features, tumors that were ER+ PR+; ER+ PR- and ER- PR+ behaved in a similar way, whereas ER- PR- tumors were different from the rest because fewer expressed bcl-2 (p = 0.0000) and had a greater expression for p53 (p = 0.009) and MIB-1/Ki-67 (p = 0.05). No significant differences were found between the four populations in recurrence rate or metastases, nor overall survival. In conclusion, these findings show that tumors that are ER- PR+ might have biological characteristics somewhere in between ER+ PR+ and ER- PR+.
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The relationship between nuclear area and the expression of estrogen (ER) and progesterone receptors (PR) was evaluated in a series of 66 breast carcinomas (50 primaries, 16 metachronous recurrences). Nuclear measurements were directly performed on touch imprints previously reacted for ER and PR by the immunocytochemical method. Nuclei expressing ER or PR were found to be smaller than negative ones. Moreover, area values of PR+ nuclei overlapped with those of ER+ ones. The pattern of receptor expression co-existence was observed to be closely related to nuclear dimensions, since a significant increase in mean nuclear areas was detected in cells from ER-/PR-tumours, as compared with cells from ER+/PR+, ER+/PR- and ER-/PR+ sub-groups. Nuclear area values were also determined in both steroid receptor-positive and steroid receptor-negative neoplastic cells co-existing in the same breast carcinoma. No significant differences in nuclear area values were found between receptor-positive and receptor-negative neoplastic cells in tumours featuring a positive status for at least one of the steroid receptors (ER+/PR+, ER+/PR- or ER-/PR+). On the contrary, in breast carcinomas characterized by a negative steroid receptor status (ER-/PR-), receptor-negative neoplastic nuclei were significantly larger than receptor-positive ones. It is suggested that heterogeneous steroid receptor expression may be caused by a completely different pathogenetic mechanism in receptor-positive and receptor-negative breast carcinomas.
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