Immunoexpression Of Progesterone Receptor Research Articles

Interplay Between Western Diet and Mammary Cancer: Data from a Chemically-induced Model in Wistar Rats.

This study aimed to investigate the influence of Western diet on mammary cancer in Wistar female rats, focusing on systemic responses and tumor development. Twenty-eight Wistar female rats were acclimatized and divided into four experimental groups (n=7 each): Western diet (WD), Western diet with N-methyl-N-nitrosourea (MNU) administration (WD+MNU), standard diet (CTR), and standard diet with MNU administration (CTR+MNU). MNU was administered intraperitoneally at 50 mg/kg at seven weeks of age to induce mammary cancer. The 20-week experiment involved monitoring animal weight, food and water intake. At the end of the study, rats were euthanized, and blood samples and organs were collected for hematological and plasma biochemical analysis, oxidative stress, and histo-pathological and immunobiological evaluations of the tumors. No significant differences were found in body weight, composition, or organ weights, but the WD group showed reduced food and water intake and lower cholesterol levels. Leptin and adiponectin levels were higher in the WD+MNU group, suggestive of changes in appetite regulation. Histopathological analysis showed malignant tumors in both MNU-induced groups. However, WD groups had fewer tumors compared to the CTR+MNU group. WD led to higher feed efficiency and increased visceral adipose tissue but decreased systemic cholesterol and triglyceride levels. While this diet resulted in lower tumor incidence, the volume and weight of the tumors were higher. Additionally, the WD decreased ERα and progesterone receptor immunoexpression, while Ki-67 immunoexpression was elevated.

Estrogen and Progesterone Receptor Immunoexpression in Fallopian Tubes among Postmenopausal Women Based on Time since the Last Menstrual Period.

Existing data on the expression of estrogen receptor (ERα) and progesterone receptor (PR) in fallopian tubes in postmenopausal women are mostly inconclusive. Therefore, we assessed ERα and PR immunoexpression in the oviducts of these women. One hundred postmenopausal women were divided into three groups based on time elapsed since the last menstrual period: (A) 1–5 years, (B) 6–10 years, and (C) ≥11 years. In all groups, both in the glandular epithelium and stroma of the ampulla and isthmus of the oviduct, immunolocalization of ERα and PR were noted. The glandular epithelium of the ampulla showed a higher percentage of PR-positive cells than the isthmus in each group. Regarding ERα, there were no significant differences. In the glandular epithelium in both the ampulla and isthmus, the percentage of ERα- and PR-positive cells was significantly higher than that in the stroma in each study group and higher in the A group than in the C group. In conclusion, in postmenopausal women, time elapsed since the last menstrual period in the fallopian tubes was positively correlated with the following: (1) the epithelium showed vacuolation of cytoplasm with greater frequency, (2) the proportion of ciliated cells decreased, and (3) the percentage of ERα- and PR-positive cells also decreased. The obtained results indicate a significant decrease in ERα and PR expression depending on the time that has elapsed since the last menstruation, which is undoubtedly related to the loss of the reproductive function of the patients.

Insights into molecular pathways of endometriosis and endometriosis-related ovarian carcinoma.

Background: Endometriosis is a benign estrogen-dependent gynecological disease involving components of the female genital tract (uterus, Fallopian tubes, ovaries, large, round, and utero-sacral ligaments) and intra- and extraperitoneal regions. Since the moment of its etiopathogeny has been identified, the intrinsic capacity of endometriosis malignant transformation has been hypothesized. Patients, Materials and Methods: Our study included a total number of 50 patients diagnosed with endometriosis (31 cases) and endometriosis-related ovarian carcinoma (EOC) (19 cases). A clinicopathological and immunohistochemical study directed towards the detection of atypical transition lesions and the similitudes in epithelial–mesenchymal transition (EMT) phenomenon [E-cadherin/β-catenin/cytokeratin 18 (CK18)], apoptosis [B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X (Bax)], and hormonal dynamics mirrored by the immunoexpression of estrogen receptor (ER) and progesterone receptor (PR) in endometriosis and EOC glands and stroma has been performed. Results: Our study showed a higher immunoexpression of CK18 and E-cadherin in endometriosis than in neoplastic counterparts, while β-catenin had a stronger immunoexpression in tumors compared with endometriotic areas, with statistically significant differences between the studied groups. Bcl-2/Bax higher rate in endometriosis had a statistically significant association to a more aggressive tumor behavior (p=0.020). ER immunoexpression was stronger in endometriosis, with less negative scores compared to EOC, while PR immunoexpression was stronger in endometriosis, with a lower percent of negative scores compared to EOC. PR immunostaining was correlated to ovarian location of endometriosis (p=0.004) and tumor grade of EOC (p=0.027). Stromal ER and PR immunoexpression has been significantly lower in endometriosis in comparison to tumor stroma (p=0.001) and PR stromal immunoexpression had been higher in more differentiated tumors compared to less differentiated types (p=0.005). Conclusions: Our study supports that endometriosis is a precursor of EOC by the identification and the coexistence of both lesions in the investigated cases, the identification of intermediate lesions, as well as the expression of EMT immunomarkers, along with apoptosis and steroid receptors immunoexpression.

Markers of Cellular Proliferation, Apoptosis, Estrogen/Progesterone Receptor Expression and Fibrosis in Selective Progesterone Receptor Modulator (Ulipristal Acetate)-Treated Uterine Fibroids.

There appear to be very few data on the exact mechanisms of a selective progesterone receptor modulator action in myomas. The aim of the study was to assess the effects of ulipristal acetate (UPA) on fibroids, especially on estrogen receptor (ER) and progesterone receptor (PR) immunoexpression, proliferation, apoptosis and tissue fibrosis, and to compare the above parameters in untreated (surgical attention only) and UPA-treated leiomyomas. UPA-treated patients were divided into three groups: (1) good response (≥25% reduction in volume of fibroid), (2) weak response (insignificant volume reduction) and (3) no response to treatment (no decrease or increase in fibroid volume). The study observed a significant decrease in the percentage of collagen volume fraction and ER and PR immunoexpression in the good response group, in the percentage of proliferating cell nuclear antigen (PCNA)- and Ki67-positive cells in the groups with good and weak reactions vs. control group; significantly higher apoptotic index (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells) in the good reaction group vs. control group. The results of the study indicate that a good response to UPA, manifested by a volume reduction of myoma, may be associated with a decrease in fibrosis, ER/PR and PCNA and Ki67 immunoexpression and an increase in cell apoptosis within the myoma.

Immunoexpression of progesterone receptor, epithelial growth factor receptor and galectin-3 in uterine smooth muscle tumors

Uterine smooth muscle tumors constitute a spectrum of neoplasms. Diagnosis of leiomyomas (LMs) is usually straight forwards; however, atypical leiomyomas (ALMs) and smooth muscle tumors of uncertain malignant potential (STUMPs) have overlapping features and need to be distinguished from leiomyosarcoma. To evaluate progesterone receptor (PR), epithelial growth factor receptor (EGF-R), and galectin-3 expression in LMs, ALMs, STUMPs, and leiomyosarcomas and to assess their possible role in differentiating those tumors. Immunoexpression of EGF-R, PR, and galectin-3 were studied in 44 cases of uterine smooth muscle tumors through retrospective study. Studied cases included 20 LM, 9 ALM, 5 STUMP, and 10 leiomyosarcomas. A semiquantitative score was used to evaluate immunohistochemical staining. EGF-R overexpression was detected in leiomyosarcomas while a lack of or reduced EGF-R expression was observed in the nonsarcomatous group (LMs, ALMs, and STUMPs) with a highly significant difference. On the contrary, there was weak or negative PR staining in leiomyosarcomas compared to intense PR expression in the nonsarcomatous group with a highly significant difference. Meanwhile, galectin-3 was downregulated in leiomyosarcomas compared to the nonsarcomatous group with a significant difference. Correlation analysis revealed negative correlation between EGF-R and PR expression with significant statistical results while correlation of galectin-3 with EGF-R and PR showed insignificant statistical results. Immunoexpression of EGF-R, PR, and galectin-3 could help differentiate challenging cases of uterine smooth muscle tumors. Further studies are recommended to investigate interactions between EGF-R, PR, and galectin-3 and to plan new therapeutic strategies.

Evaluation of 1p and 14q status, MIB-1 labeling index and progesterone receptor immunoexpression in meningiomas: Adjuncts to histopathological grading and predictors of aggressive behavior.

Meningiomas are benign central nervous system tumors; however, significant fraction recurs, irrespective of histological grade. We performed fluorescence in-situ hybridization for 1p36 and 14q32, and immunohistochemistry for progesterone receptor (PR), p53 and MIB-1 on 84 meningiomas. Sixty-four were convexity tumors (30 grade I, 21 grade II, 13 grade III) and 20 petroclival (grade I; 10 with gross total resection (GTR), 10 with subtotal resection (STR)). Isolated 1p36 deletion was seen in 20% grade I, 28.6% grade II and 30.8% grade III convexity meningiomas, and isolated 14q deletion in one grade III convexity tumor. 1p/14q co-deletion was seen in none of grade I, 28.5% grade II and 30% grade III convexity meningiomas. PR immunoreactivity was less frequent in grade III tumors. Petroclival tumors did not show isolated deletion. However, 1p/14q co-deletion was seen in 20% of petroclival tumors with STR and in none with GTR. Frequency of chromosomal alterations and MIB-1 labeling index both increase with tumor grade. 1p/14q co-deletion is characteristic of grade II/III meningiomas, while PR immunoreactivity inversely correlates with grade, suggesting their use as surrogate markers for grading. Identification of 1p/14q co-deletion in grade I petroclival tumors with STR suggests that unresectable petroclival meningiomas are biologically more aggressive than their grade I convexity counterparts.

Clinicopathological characteristics, hormone receptor status and matrix metallo-proteinase-9 (MMP-9) immunohistochemical expression in spinal meningiomas

Meningiomas involving the spinal meninges show a reduced tendency to recur compared to those of the intracranial compartment. Nonetheless, due to the few reports with a significant number of patients, their biological characteristics largely remain to be investigated.With the aim of clarifying the biology of these tumors, we examined in the present paper the clinicopathological features, the estrogen receptor (ER) and progesterone receptor (PR) status, as well as the Ki-67 labeling index (LI) and matrix metallo-proteinase-9 (MMP-9) expression of 58 spinal meningiomas. Ki-67 LI ranged between 1% and 5% (median: 1%); no expression of ER was found in all the cases, whereas PR immunoexpression was found in 86% of the tumors. High MMP-9 expression was encountered in 46% of meningiomas, and it was significantly correlated with the percentage of PR expression. The recurrence rate was 1.7%. The only recurred case showed high MMP-9 expression, absence of PR and low Ki-67 LI.Our findings confirm that spinal meningiomas are indolent tumors with low growth fraction and recurrence rate. In these neoplasms, high MMP-9 expression seems to be associated with the development of recurrences only in the absence of PR expression. Thus, the evaluation of both MMP-9 and PR expression might be of use in the identification of spinal meningiomas at higher risk of relapse.

Analysis of the expression of estrogen receptor, progesterone receptor and chicken ovalbumin upstream promoter-transcription factor I in ovarian epithelial cancers and normal ovaries

Sex hormones are involved in the carcinogenesis of some gynecologic cancers, and the status of their receptors represents an indicator of prognosis and of the therapeutic response in breast and endometrial cancers. In the ovary, this role is not clearly defined, with epithelial cancers being poorly responsive to hormone therapy. COUP-TFI (chicken ovalbumin upstream promoter-transcription factor I) is an orphan nuclear receptor, which is expressed in various tissues and regulates the estrogen receptor (ER) by competition for DNA binding. To investigate the role of these receptors in ovarian carcinogenesis and their implications for cancer prognosis, we evaluated the immunohistochemical expression of ER, progesterone receptor (PR) and COUP-TFI in benign and malignant ovarian epithelial neoplasms and in normal ovaries. A total of 113 ovarian specimens, including 40 diagnosed as malignant epithelial neoplasms (group A), 45 as benign epithelial tumors (group B), and 28 from normal ovaries (group C) were analyzed. Immunoexpression of ER was observed in 70% of patients of group A, 57.8% of group B and 57.1% of group C, with no significant difference between groups (p=0.426). Immunoexpression of PR was significantly lower in group A (12.5%) compared to group B (42.2%) and group C (32.1%) (p=0.010). Similarly, COUP-TFI was expressed in only 10% of group A patients, a rate significantly lower than that observed for group B (31.1%) and group C (39.3%) (p=0.014). No association was observed between the expression of these markers and increased survival or clinical prognostic variables. Multivariate analysis revealed a residual tumor <1 cm as the most significant clinical prognostic factor in group A (p=0.010, OR=4.14). These data support the importance of cytoreduction in the treatment of ovarian cancer, the role of steroid receptors in the mechanism of carcinogenesis, and the need for selection of subgroups that may respond to hormone therapy.

Estrogen and Progesterone Receptor Expression in Uterine and Extrauterine Leiomyosarcomas

The authors have noted anecdotal cases of extrauterine leiomyosarcomas (LMS) with estrogen receptor (ER) and progester-one receptor (PR) immunoreactivity. However, there are few studies that have compared ER and PR immunoexpression in LMS of uterine and extrauterine origin. The authors obtained a representative formalin-fixed, paraffin-embedded tissue block from cases of uterine LMS (n = 15) and extrauterine LMS (n = 16) from the archives of the Cleveland Clinic Foundation and performed immunohistochemical staining for ER and PR. Staining was evaluated by 2 observers in a semiquantitative manner using the following scale: 0, no nuclear staining; 1+, 1 to 25% of nuclei stained; 2+, 26 to 50% of nuclei stained; 3+, 51 to 75% of nuclei stained; 4+, 76 to 100% of nuclei stained. The majority of uterine LMS stained for ER (13 of 15, 87%), PR (12 of 15, 80%), or both ER and PR (12 of 15, 80%), with most cases showing 3+ or 4+ positive staining. For the extrauterine LMS cases, staining for ER was seen in 4 of 16 cases (25%), staining for PR was observed in 2 of 16 cases (13%), and staining for both ER and PR was seen in 2 of 16 cases (13%). One extrauterine LMS showed 4+ coexpression of ER and PR, but the remaining extrauterine cases showed only 1+ ER and/or PR immunoreactivity. These data suggest that most uterine LMS coexpress ER and PR, and most extrauterine LMS do not stain for these antigens. However, a subset of extrauterine LMS are ER and/or PR immunoreactive. This raises the possibility that hormonal manipulation may be beneficial in the treatment of these therapeutically recalcitrant tumors.

Relationship between expression of sex steroid receptors and structure of the seminal vesicles after neonatal treatment of rats with potent or weak estrogens.

In this study we evaluated the effect of manipulating the estrogen and androgen environment of the neonatal male rat on subsequent immunoexpression of sex steroid receptors in the seminal vesicles (SVs) at age 18 days. The aim was to establish to what extent such changes were associated with and predictive of changes in SV structure/composition. Treatments were either diethylstilbestrol (DES; 10, 1, or 0.1 microg/injection), ethinyl estradiol (EE; 10 microg/injection), tamoxifen (2 mg/kg/day), flutamide (50 mg/kg), a gonadotropin-releasing hormone antagonist (GnRHa; 10 mg/kg), genistein (4 mg/kg/day), octylphenol (2 mg/injection), or bisphenol A (0.5 mg/injection). Compared with controls, treatment with DES (10 microg) induced loss of epithelial and stromal androgen receptor (AR) immunoexpression coincident with induction of stromal progesterone receptor (PR) immunoexpression and upregulation of stromal immunoexpression of estrogen receptor-alpha (ERalpha). These changes were associated with gross distortion (increase) of the normal stromal:epithelial tissue proportions in the SVs. DES (1 microg) and EE induced similar but less pronounced changes, and DES (0.1 microg) had no noticeable effect. Tamoxifen and flutamide induced PR and slightly upregulated ERalpha immunoexpression but had only a minor or no effect on AR expression and the stromal:epithelial ratio, though flutamide retarded normal development of the SVs. The latter was also evident in GnRHa-treated males, but otherwise this treatment had no effect on AR and PR immunoexpression. None of the foregoing treatments had any detectable effect on the immunoexpression of ERss in stromal or epithelial cells. The major treatment-induced changes in immunoexpression of AR, PR, and ERalpha and lack of change in ERss were confirmed by Western blots of SV protein extracts. None of the three weak (environmental) estrogens tested caused any detectable change in sex steroid receptor immunoexpression or SV tissue composition. We conclude that treatment-induced loss of AR is a prerequisite for altered stromal:epithelial proportions in the SVs and that such loss is always associated with induction of PR and upregulation of ERalpha; the latter two changes are insufficient on their own to bring about such a change. Nevertheless, induction of PR expression was always associated with altered SV development and is a potentially useful marker because it is not normally expressed in male reproductive tissues.

Endometrial Response to Sexual Steroids as Assessed by Prostaglandin F2α Output in Explant Culture and Hormone Receptor Expression

The objective of this study was to evaluate the endometrial response to sexual steroids in organ culture using two means: prostaglandin (PG) F_2α output in medium culture and steroid receptor immunoexpression in tissue. Human endometrium samples were classified in homogeneous and heterogeneous proliferative or secretory subsets. In proliferative endometrium explant culture, progesterone (10^–7 M) induced a significant decrease in PGF_2α output, but this was not the case in secretory endometrium, whereas no significant effect of estradiol (10^–8 M) was observed. Before culture, homogeneous and heterogeneous proliferative endometrium presented the same pattern of estradiol receptor (ER) and progesterone receptor (PR) expression evaluated by quantitative immunocytochemistry. After culture, immunoreactive ER and PR were detected on the explant. PR immunoexpression rates after culture were lower than before culture in glands on homogeneous proliferative and in stroma on heterogeneous proliferative endometrium explants without in vitro steroid addition. In secretory endometrium, no significant difference was observed between ER or PR immunoexpression rates before culture and after culture. These results provided the hormonal receptivity status of endometrium after culture and will thus serve as a reference for evaluating in vitro steroid effects on endometrium explants. Our preliminary results suggest that cultures of endometrium explants are a valid model for studying the effects of hormonal treatment on homogeneous as well as heterogeneous endometrium. These data could be particularly relevant for evaluating the potential response to hormone stimulation and treatment of endometria sampled in perimenopausal patients.

Induction of progesterone receptor immunoexpression in stromal tissue throughout the male reproductive tract after neonatal oestrogen treatment of rats

Oestrogen exposure of the male during fetal/neonatal life can fundamentally alter the structure and function of the reproductive system, though how is unknown. This study examined whether such treatment was able to induce a ‘female’ characteristic, namely immunoexpression of progesterone receptor (PR), in the reproductive system of the male. Rats were treated on postnatal days 2, 4, 6, 8, 10 and 12 with either 10, 1 or 0.1 μg diethystilbestrol (DES) or with the vehicle (20 μl corn oil). Groups of control and treated rats were killed on days 18, 25, 35 and 90 (=adults) and tissues fixed in Bouins for immunolocalisation studies using antisera to PR (recognises A and B forms) and oestrogen receptor- β (ER β). PR immunoexpression was absent from all tissues studied in control rats at all ages with the exception of the parasympathetic ganglia of the prostate. In rats treated with 10 μg DES, intense immunoexpression of PR was detected in the nuclei of stromal, but not epithelial, cells of the caput and cauda epididymis, the vas deferens, seminal vesicles and at the base of the dorsolateral prostatic complex (DLPC) at day 18, but was absent from the ventral prostate and from the testis. DES induction of PR immunoexpression was evident after a single injection (on day 3) and at 18–35 days the intensity of immunoexpression was DES dose-dependent; rats treated neonatally with 0.1 μg DES showed no detectable PR immunoexpression at any age. These findings were confirmed by Western analysis which indicated that most of the PR induced was probably the B form. Co-localisation studies, using confocal microscopy, demonstrated that PR and ER β frequently co-localised to the same stromal cells in the DLPC, epididymis and seminal vesicles of DES-treated rats at day 18, whereas epithelial cells, which also expressed ER β, did not express PR. In the tissues studied, only occasional stromal cells expressed ER α in comparison to the more widespread expression of ER β, although epithelial cell expression of ER α was also detected in the epididymis on day 18 (but not on day 10). In DES-treated rats, immunoexpression of PR in the reproductive tract decreased progressively in intensity from days 18–35 and was non-detectable in adulthood. In conclusion, these findings are interpreted as evidence that neonatal oestrogen treatment exerts pervasive ‘reprogramming’ effects throughout the reproductive system of the developing male as indicated by the induction of PR immunoexpression. This induction was restricted to stromal tissue even though both stromal and epithelial cells at most sites expressed ER β and/or ER α.

Immunohistochemical Profile of Endometrial Adenocarcinoma: A Study of 61 Cases and Review of the Literature

The differences in immunohistochemical expression of p53, bcl-2, bax, estrogen receptor (ER), and progesterone receptor (PR) were evaluated in 40 endometrioid and 21 papillary serous carcinomas of endometrium and correlated with known predictors of survival, such as grade and stage. Uterine papillary serous adenocarcinomas (UPSA) showed significantly higher p53 expression than did uterine endometrioid adenocarcinomas (UEA) (76.2% versus 35%), whereas both ER and PR were more often positive in endometrioid than in serous tumors (p =.005 and.0005). No significant difference was found in bcl-2 and bax expression between both histologic types. However, there was definite decrease in intensity of bcl-2 in UPSA compared with UEA. In endometrioid carcinoma, p53 overexpression was associated with high-grade and advanced-stage tumors (p =.0006 and.006), whereas ER and PR expression was associated with low-grade and early-stage tumors (p =.0006 and.0001; p =.003 and.0006). Bcl-2 immunopositivity was more common in low-grade, early-stage rather than in high-grade, advanced-stage adenocarcinomas, but the difference was not statistically significant (p =.24 and.07). Bax immunopositivity was associated with well-differentiated (p =.04) and early-stage tumors. Furthermore, a significant inverse relationship between bax and p53 reactivity was defined (p =.05), especially in tumors of endometrioid type. Bax and PR immunoexpression correlated near the limit of statistical significance (p =.08), whereas no relationship was found among bax, bcl-2, and ER immunopositivity. Our results indicate that the differences in immunohistochemical profiles of endometrioid and serous carcinomas support the existence of different molecular pathways of their development. The correlation of immunohistochemical findings with histologic grade and clinical stage could help in predicting biologic behavior and planning treatment in patients who are diagnosed as having these tumors.