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Results for “PGR expression”

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PubMed1998

Immunohistochemical study of hormone receptor and hormone-regulated protein expression in phyllodes tumour: comparison with fibroadenoma.

The histogenesis of phyllodes tumour (PT) and that of fibroadenoma (FA) of the breast appear to be closely related. FA is thought to be hormonally responsive, while the hormone-responsiveness of PT is uncertain. To gain insight into hormone-responsiveness of PT, we performed immunohistochemical analysis of oestrogen-regulated pS2 and androgen-regulated prostate-specific antigen (PSA) protein expression and also of oestrogen receptor (ER), progesterone receptor (PgR) and androgen receptor (AR) expression in paraffin sections obtained from 50 female PT patients. Paraffin sections taken from 50 female fibroadenoma (FA) patients were analysed for comparison. ER, PgR, pS2, AR and PSA expression were detected in 32%, 96%, 20%, 98% and 4.0% of PT sections and in 28%, 96%, 42%, 80% and 10% of FA sections, respectively. No correlations were detected among ER, PgR and pS2 expression or between AR and PSA expression in PT or FA sections. PgR expression was significantly associated with AR expression in PT (P<0.0001). The present investigations indicate that PT and FA have almost similar hormone receptor status. However, different positivities of pS2 expression suggest that oestrogen-responsiveness may differ between PT and FA. In addition, a wide-ranging co-expression of AR and PgR in PT sections suggests that these receptors may play an important part in the proliferation, although the functional significance of these receptors should be elucidated.

Adolescent↗

PubMed2005

Null mutation of Kruppel-like factor9/basic transcription element binding protein-1 alters peri-implantation uterine development in mice.

Female mice null for the basic transcription element binding protein-1 (Bteb1) gene have reduced numbers of implanting embryos. We hypothesized that the implantation defect, resulting in subfertility, is a consequence of developmental asynchrony between the embryo and uterine endometrium at peri-implantation. To address this, endometrium from wild-type (WT) and Bteb1(-/-) females at 0.5 to 5.5 days postcoitum (dpc) were evaluated for proliferation (BrdU labeling), apoptosis (TUNEL), and steroid hormone receptor expression (immunohistochemistry). Loss of BTEB1 did not affect serum estrogen (E) and progesterone (P) levels. In stroma (ST), the numbers of progesterone receptor (PGR) and HomeoboxA10 (HOXA10)-expressing cells were lower (3.5 and 4.5 dpc), while those of estrogen receptor-alpha (ESR1) were higher (3.5 dpc), with Bteb1 ablation. The peak of proliferation in luminal epithelium (LE), glandular epithelium (GE), and ST was delayed, while the apoptotic index in all cell types was increased (2.5 dpc) in Bteb1(-/-) relative to WT mice. The numbers of PGR-positive ST cells was negatively correlated with LE proliferation in WT mice; this correlation was lost in Bteb1(-/-) mice and was not observed before 2.5 dpc for both genotypes. Proliferation and apoptosis in all endometrial compartments, as well as the numbers of PGR-, HOXA10-, and ESR1-expressing ST cells, were lower in Bteb1(-/-) relative to WT mice after ovariectomy and E + P treatment. Results suggest that BTEB1, by regulating ST PGR expression and transactivation, participates in the paracrine control of LE proliferation by PGR and thus is important for establishment of a receptive uterus critical for successful implantation.

Animals↗

PubMedDate not supplied

Insulin-like growth factor II (IGF-II) immunohistochemistry in breast cancer: relationship with the most important morphological and biochemical prognostic parameters.

Recent in situ hybridization experiments have shown a high content of IGF-II mRNA in breast cancer stroma. The aim of this study was to examine the relationship between IGF-II protein expression and several prognostic parameters in 75 infiltrating ductal carcinomas (IDC) of the breast. Tissue sections were evaluated for proliferative activity, IGF-II protein, ER, PgR, p53, and p21 expression using immunohistochemical procedures. The degree of stromal proliferation was assessed. Menopausal status, axillary lymph node involvement and nuclear grade were known. Thirty-five patients (44.3%) were premenopausal and 47 (62.6%) had lymph node metastases. Marked stromal proliferation was found in 34 (45.3%) specimens and high nuclear grade in 20 (26.5%). Eighteen tumors (24%) showed no IGF-II immunostaining. In the positive cases, IGF-II was detected both in the tumor stroma and in the cytoplasm of epithelial cancer cells: a high IGF-II content was found in 12 specimens (16.0%), a low content in 14 (18.7%) and a moderate content in 31 (41.3%). Twenty-four tumors (32.0%) showed high proliferative activity. Both ER and PgR were expressed in the nucleus of cancer cells: 49 tumors (65.3%) were ER positive (ER+) and 34 (45.3%) PgR positive (PgR+). p21 protein was detected in 37 tumors (49.6%) and p53 in 12 (16%). IGF-II protein was not correlated with menopausal status, lymph node metastases, nuclear grade, proliferative activity, ER or p53. In contrast, IGF-II correlated strongly with stromal proliferation (p=0.008), PgR (p=0.03) and p21 (p=0.01). This study demonstrates that in IDC of the breast IGF-II protein is expressed in the epithelium and stroma of the majority of tumors and is correlated with stromal amount, PgR and p21 expression. These preliminary results indicate that IGF-II expression in breast cancer is connected with two important regulators of breast cancer growth and differentiation.

Adult↗

PubMed1996

[Dna synthesis and expression of steroid receptors in cells of human breast carcinoma].

In order to observe receptor expression (ER and PgR) in human breast cancer cells during the S-phase of the cellular cycle, we evaluated 21 tumoral samples using a double labeling immunocytochemical-autoradiographic assay. In 16 of these we have verified that expression of ER and PgR is not influenced by incubation with 3H-Thymidine for 60 minutes. The results also demonstrated that receptor expression during the S-phase is more common in postmenopausal tumors and is principally dependent on percentages of ER+ (p < 0.01) and PgR+ (p < 0.01) cells; moreover, proliferative activity occurs almost exclusively in ER- (p = 0.003) and Pgr- (p = 0.001) cellular sub populations and the presence of PgR, but not of ER, is related to arrest of DNA synthesis (p = 0.02).

Adult↗

PubMed1994

Ki-67 staining in benign, borderline, malignant primary and metastatic ovarian tumors: correlation with steroid receptors, epidermal-growth-factor receptor and cathepsin D.

Ki-67 immunoreactivity was studied in relation to immunohistochemically assessed expression of epidermal-growth-factor receptor (EGFR), estrogen receptor (ER) progesterone receptor (PgR) and cytosolic levels of cathepsin D in advanced human ovarian adenocarcinomas, borderline and benign cystadenomas and normal ovaries. A significantly higher number of Ki-67-positive cells were found in metastatic tumors vs. primary adenocarcinomas and in the total group of adenocarcinomas vs. benign/borderline cystadenomas. Cathepsin-D levels were also significantly higher in metastatic tumors than in primary adenocarcinomas, which in turn presented higher levels than were found in normal ovaries. However, no significant difference was observed between cathepsin-D levels in malignant adenocarcinomas and borderline/benign cystadenomas. Immunohistochemically assessed expression of ER and PgR was detected in variable percentages of epithelial tumor cells, and stromal cells were occasionally positive as well. In the group of primary adenocarcinomas, 46% were ER-positive and 34% were PgR-positive, although there was no significant difference between primary and metastatic lesions with respect to ER or PgR expression. Concordance between immunohistochemically assessed ER or PgR data and cytosolic ER and PgR levels measured with enzyme immunoassay was relatively low. EGFR, immunohistochemically assessed with MAb-EGFRI, was positive in 76% of the primary and in 78% of the metastatic adenocarcinomas. A strong positive association was detected between ER and PgR, and EGFR was observed to present a weak positive correlation with Ki-67 and ER. Cathepsin-D levels were not found to be significantly correlated with the expression of ER, PgR, EGFR or Ki-67.

Adenocarcinoma↗

PubMed2005

Difference in progesterone-receptor isoforms ratio between early and late first-trimester human trophoblast is associated with differential cell invasion and matrix metalloproteinase 2 expression.

The expression profile of the progesterone-receptor isoforms and progesterone regulation of matrix metalloproteinase 2 (MMP2) were investigated in early and late first-trimester trophoblast cells. Human trophoblast cells were obtained from legal abortions (6-12 wk of gestation). Purity of 95-98% was verified using immunohistochemistry with specific antibodies. Evaluation of cell count was performed with XTT Reagent kit, and invasion was tested using Matrigel invasion assay. Zymography was used to detect proteolytic activity, and Western blot immunoassay was used to study protein concentration. Gene expression of PGRB, PGR, and MMP2 was studied using reverse transcription-polymerase chain reaction with the housekeeping gene GAPDH used for normalization. Promoter activity was determined using luciferase reporter assay. Differential progesterone-receptor profile was documented with the dominance of PGRB in early trophoblast and the dominance of PGRA in late trophoblast. This differential profile is compatible with the inverse effect of progesterone on the two cell populations, decreasing invasion and gelatinase expression in the early first-trimester trophoblast and increasing invasion and gelatinase expression in the late first-trimester trophoblast. A decrease in MMP2 promoter activity in early trophoblast cells exposed to progesterone suggests that MMP2 expression is regulated by progesterone at the transcriptional level as well. Early trophoblast cells transfected with expressing vector for PGR encoding PGRA revealed less MMP2 activity and reversal of its response to progesterone similar to the effect observed in late trophoblast cells.

Embryo Implantation↗

PubMed1993

Expression and prognostic significance of estrogen and progesterone receptors in adenocarcinoma of the uterine cervix. An immunocytochemical study.

BACKGROUND: Adenocarcinoma of the uterine cervix typically is an aggressive neoplasm with a propensity for early invasion and dissemination. Little data are available correlating histologic, histochemical, or immunocytochemical parameters with the biologic behavior of this neoplasm. Specifically, the implication of expression of estrogen and progesterone receptors in cervical adenocarcinoma is essentially undefined. METHODS: An immunocytochemical hormone receptor assay using specific monoclonal antibodies against estrogen receptors (ER) and progesterone receptors (PgR) was used to study paraffin-embedded specimens from 54 patients with primary cervical adenocarcinomas. The specimens were evaluated for heterogeneity and intensity of staining. An attempt also was made to study the relationship between the pattern of hormone receptor expression and other established prognostic indicators. RESULTS: In all patients, diffuse positive staining of benign endocervical epithelial or stromal cells was observed. Positive immunostaining was seen in the adenocarcinoma specimens of 16 of 54 (30%) patients for ER and 19 of 54 (35%) patients for PgR. Expression of ER and PgR statistically correlated with each other (P = 0.0001). Endocervical-type adenocarcinoma had the highest degree of staining for both ER and PgR. Clear cell carcinomas and intestinal-type carcinomas were negative for both receptors. Positivity for ER and PgR inversely correlated with histologic grade as defined by the International Federation of Gynecology and Obstetrics (FIGO). The relationship between hormone receptor expression and FIGO stage was not statistically significant. Survival was associated with clinical stage (P = 0.004) and with immunocytochemical status of ER expression (P = 0.032) and PgR expression (P = 0.009). CONCLUSIONS: This study of 54 specimens from patients with cervical adenocarcinoma suggests that positive expression of ER and PgR is associated with prolonged survival.

Adenocarcinoma↗

PubMed2003

Letrozole inhibits tumor proliferation more effectively than tamoxifen independent of HER1/2 expression status.

BACKGROUND: The biological basis for the superior efficacy of neoadjuvant letrozole versus tamoxifen for postmenopausal women with estrogen receptor (ER)-positive locally advanced breast cancer was investigated by analyzing tumor proliferation and expression of estrogen-regulated genes before and after the initiation of therapy. METHODS: Tumor samples were obtained at baseline and at the end of treatment from 185 patients participating in a double blind randomized Phase III study of neoadjuvant endocrine therapy. These paired specimens were simultaneously analyzed for Ki67, ER, progesterone receptor (PgR), trefoil factor 1 (PS2), HER1 (epidermal growth factor receptor), and HER2 (ErbB2 or neu) by semiquantitative immunohistochemistry. RESULTS: The treatment-induced reduction in geometric mean Ki67 was significantly greater with letrozole (87%) than tamoxifen (75%; analysis of covariance P = 0.0009). Differences in the average Ki67 reduction were particularly marked for ER-positive tumors that overexpressed HER1 and/or HER2 (88 versus 45%, respectively; P = 0.0018). Twenty-three of 92 tumors (25%) on tamoxifen and 14 of 93 on letrozole (15%) showed a paradoxical increase in Ki67 with treatment, and the majority of these cases was HER1/2 negative. Letrozole, but not tamoxifen, significantly reduced expression of the estrogen-regulated proteins PgR and trefoil factor 1, regardless of HER1/2 status (P < 0.0001). ER down-regulation occurred with both agents, although levels decreased more with tamoxifen (P < 0.0001). CONCLUSION: Letrozole inhibited tumor proliferation to a greater extent than tamoxifen. The molecular basis for this advantage appears complex but includes possible tamoxifen agonist effects on the cell cycle in both HER1/2+ and HER1/2- tumors. A pattern of continued proliferation despite appropriate down-regulation of PgR expression with estrogen deprivation or tamoxifen was also documented. This observation suggests the estrogenic regulation of proliferation and PgR expression may be dissociated in endocrine therapy resistant cells.

Antineoplastic Agents, Hormonal↗

PubMed2025

Exploration of the mechanism of the Mongolian medicine Tonglaga-5 (-5) for the treatment of n-methyl-n'-nitro-n-nitrosoguanidine-induced chronic atrophic gastritis based on network pharmacology and metabolomics.

OBJECTIVE: To explore the mechanism of Tonglaga-5 (-5, TLG-5) for the treatment of chronic atrophic gastritis (CAG), based on network pharmacology and metabolomics. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into six groups (n = 8): control group; model group; teprenone group, and low-, median-, and high- dose TLG-5 groups. The enzyme linked immunosorbent assay (ELISA) was used to measure the expression of pepsinogen Ⅰ (PG Ⅰ), pepsinogen Ⅱ (PG Ⅱ) and gastrin-17 (G-17) in the serum. Hematoxylin and eosin staining were performed to observe the pathological condition. And the network pharmacology was employed to identify the targets and signaling pathways of TLG-5 affecting CAG. Then, the metabolomics approach was applied to explore the specific metabolites and metabolic pathways. Finally, validation was performed using the "metabolite-gene" interaction network, molecular docking and quantitative real-time polymerase chain reaction (qPCR). RESULTS: High-dose TLG-5 significantly improved the expression of PG Ⅰ, PGR (PG Ⅰ/ PG Ⅱ) and G-17 (P < 0.05) and inhibited the expression of phosphoinositide-3-kinase regulatory subunit 2, AKT serine/threonine kinase (AKT), hypoxia-inducible factor 1-alpha (HIF-1α) (P < 0.05). Further, high-dose TLG-5 reduced the number of glands was reduced, and fibrosis with oedema and ecchymosis appeared at the base. Overlapping TLG-5 and CAG gene targets produced 270 interactive targets. The results of gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses suggested that TLG-5 could affect CAG through the predominantly cancer and inflammation-related pathways. Pyrimidine metabolism was identified as a significantly differential pathway in the mechanism of TLG-5 for treating CAG. CONCLUSIONS: TLG-5 exerts a therapeutic effect on CAG by regulating β-alanine metabolism, pyrimidine metabolism pathways, and inhibiting the PI3K-AKT signaling pathway and HIF-1 signaling pathways.

Animals↗

PubMed1998

Frequencies of Estrogen Receptor mRNAs Splice Variants in Various Human Mammary Tissues.

BACKGROUND: Several variant estrogen receptor (ER) mRNAs are present in various cell lines of human breast cancer, and are considered to be one reason for the loss of hormone dependence. The purpose of this study was to assess the ER variants in human various breast tissues, and to investigate the correlation between the expression of ER variants and ER/progesterone receptor (PgR) status. METHODS: The frequencies of 3 ER splice variants (del 2/3, del 5, and del 7) were assessed in 24 benign and 76 malignant breast lesions by the reverse transcription ]polymerase chain reaction (RT-PCR) method and compared with histopathological features. ER and PgR proteins were analyzed using enzyme immunoassay (EIA) and immunohistochemical assay (IHA) in 68 cases of cancer to determine whether aberrant variants influence the status of either protein. RESULTS: Deletions of exons 5 and 7 (del 5 and 7) were more frequent than the deletion of exon 2/3 (del 2/3) in both benign and malignant lesions, and the expression of del 5 and del 7 seemed to correlate with epithelial overgrowth. There was no significant difference between the ER/PgR protein status and the expression of each ER variant in breast cancer. CONCLUSION: The expression of ER splice variants is not uncommon in human breast diseases. The abnormal ER structures in this study are not a main factor for tamoxifen insensitivity or an important regulators of PgR expression.

Journal Article↗

PubMed1996

p53 and bcl-2 expression correlates with clinical outcome in a series of node-positive breast cancer patients.

BACKGROUND AND PURPOSE: The tumor-suppressor gene TP53 and the proto-oncogene bcl-2 encode, respectively, for a nuclear phosphoprotein and for a mitochondrial protein involved in multiple cellular functions. The proteins provide prognostic information in node-negative breast cancer and are supposed to influence treatment responsiveness. We analyzed the predictive role of p53 and bcl-2 expression, alone and in association with other variables, in postmenopausal women with node-positive, estrogen receptor-positive (ER+) breast cancers treated with radical or conservative surgery plus radiotherapy and adjuvant tamoxifen for at least 1 year. PATIENTS AND METHODS: On 240 resectable cancers, we determined the expression of p53 and bcl-2, using immunohistochemistry, cell proliferation (3H-thymidine labeling index [3H-dT LI]), and ER and progesterone receptors (PgR). RESULTS: p53 expression and 3H-dT LI were weakly related to one another and both were unrelated to bcl-2. Relapse-free and distant metastasis-free survival at 5 years were significantly lower for patients with tumors that highly expressed p53 (P = .0001) and for those that weakly expressed or did not express bcl-2 (P = .02). However, p53, but not bcl-2, provided prognostic information independent of tumor size, axillary node involvement, steroid receptors, and 3H-dT LI. Moreover, the simultaneous p53 overexpression and lack of PgR identified patients at maximum risk of relapse, whereas bcl-2 overexpression, associated with a low 3H-dT LI or the presence of PgR, improved the prognostic resolution for low-risk patients. CONCLUSION: p53 expression appears to be indicative of clinical outcome in postmenopausal patients treated with tamoxifen. Whether p53 overexpression and weak bcl-2 expression are indicators of biologic aggressiveness, regardless of treatment, or of hormone resistance remains to be defined.

Aged↗

PubMed2006

Comparison of immunohistological parameters in primary breast cancers and corresponding locoregional recurrences.

Biological changes in breast cancers during tumor progression can affect therapeutic parameters, such as hormone receptors. We studied a series of primary tumors and the matching recurrent lesions to analyze the frequency of this phenomenon and the impact on disease-free interval. The expression of ER, PgR, c-erbB2, CD44v6, and p53 in the primary and the locoregional tumor was analyzed in 70 patients with recurrent breast cancer. Antigen expression correlated well between the primary and the matching recurrent tumor for all antigens under study. However, hormone receptor expression was lost in more than 50% of the cases, without significant impact on the disease-free survival interval. The disease-free interval was significantly longer for PgR-positive primary tumors, but did not depend on the ER status. The expression or changes of c-erbB2, CD44v6, and p53 were not related to the recurrence-free time intervals. Therefore, for treatment, it seems important to consider a possible loss of hormone receptors during tumor progression.

Adult↗

PubMed1997

Constitutive co-expression of estrogen and progesterone receptor mRNA in human meningiomas by RT-PCR and response of in vitro cell cultures to steroid hormones.

Although it is well recognised that human meningiomas are rich in progesterone receptor (PgR), controversy has existed about the presence of the estrogen receptor (ER) in these tumours. We have investigated the presence of both ER and PgR in a series of 20 human meningiomas, spanning the main histological groups, using reverse transcription linked PCR (RT-PCR). Total RNA was extracted from whole tissues and reverse transcribed to yield cDNA. This was amplified using primers specifically designed to detect ER and PgR. All samples co-expressed ER and PgR mRNA, irrespective of tumour classification, patient age or sex. In general, transcripts for PgR appeared considerably stronger than those for ER, and although this was a purely qualitative study, it suggests increased expression of PgR. Addition of exogenous 17beta-estradiol or progesterone to meningioma cell cultures showed that 2/4 cultures responded to these steroids. Our results confirm that human meningiomas do express gene transcripts for ER, and that previous failures to detect ER in these tumours may be due to the lack of sensitivity of the techniques employed. However, these receptors may not be functional in all tumours.

Adult↗

PubMed2002

Immunohistochemical expression of extracellular matrix components tenascin, fibronectin, collagen type IV and laminin in breast cancer: their prognostic value and role in tumour invasion and progression.

The immunohistochemical expression of the extracellular matrix (ECM) components tenascin (TN), fibronectin (FN), collagen type IV (Coll) and laminin (LN), and their possible relationships were studied in a series of 134 operable breast cancer cases. Their expression was also compared with the expression of the proteolytic enzyme cathepsin D (CD), the adhesion molecule CD44 standard form (CD44s) and other known factors to clarify the prognostic value and role of these molecules in tumour progression and metastasis. TN expression in the tumour stroma was positively correlated with tumour grade and size, CD44s expression, tumour and stromal CD expression as well as with FN, laminin and Coll expression in the same areas. TN expression was inverse correlated with ER status. Its expression at the invasion front was only positively correlated with the lymph node status. Survival analysis showed an increased mortality risk associated with high levels of TN expression. In multivariate analysis, among the ECM proteins, only TN expression was independently correlated with patients' survival. FN expression was positively correlated with lymph node involvement, with the proliferation-associated index Ki-67 and stromal CD expression. Survival analysis showed an increased mortality risk associated with a high level of FN expression. Coll expression was positively correlated with the tumour size and LN expression. An inverse relationship of Coll expression with ER and PgR receptor status was also found. LN expression was positively correlated with tumour and stromal CD expression, with the proliferation-associated index Ki-67 and inversely with ER receptor status. The observed alterations in the expression of ECM proteins in breast cancer tissue and their correlations with the proteolytic enzyme CD and the adhesion molecule CD44s, suggest an involvement in cancer progression. In addition, overexpression of stromal TN and FN seems to have negative prognostic value in breast cancer patients.

Adult↗

PubMed2006

Progesterone regulation of human granulosa/luteal cell viability by an RU486-independent mechanism.

CONTEXT: Progesterone (P4) inhibits human granulosa/luteal cell apoptosis by an unknown mechanism. OBJECTIVE: Our objective was to assess the role of the nuclear P4 receptor (PGR) and PGR membrane component 1 (PGRMC1) in mediating P4's antiapoptotic action in human granulosa/luteal cells. DESIGN, SETTING, AND PATIENTS: In vitro laboratory studies were designed in which human granulosa/luteal cells were harvested from in vitro fertilization patients from 2004-2006. MAIN OUTCOME MEASURE: Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assays and DNA staining. Protein expression was observed by Western blot and immunocytochemistry. RESULTS: PGR was detected in 20% of the human granulosa/luteal cells, and 25 and 50 microM RU486 induced at least 70% of the cells to undergo apoptosis. Five micromolar RU486 neither induced apoptosis nor attenuated the antiapoptotic action of 1 microM P4. PGRMC1 and its binding partner, plasminogen activator inhibitor RNA-binding protein-1 (PAIRBP1), were detected in human granulosa/luteal cells. Antibodies to either PGRMC1 or PAIRBP1 completely attenuated P4's action. CONCLUSIONS: PGR does not exclusively mediate P4's action because 1) 5 microM RU486 should have been able to override the antiapoptotic action of 1 microM P4 because RU486 binds to the PGR at a greater affinity than P4; 2) 25 and 50 microM RU486 induce three to four times more cells to undergo apoptosis than express PGR; 3) P4 must be continuously present to prevent apoptosis, which implies a rapid, possibly membrane-initiated mechanism of action; and 4) expression and blocking antibody studies suggest that PGRMC1 and PAIRBP1 account in part for P4's action in human granulosa/luteal cells.

Apoptosis↗

PubMed1995

Effects of gonadal steroids on the growth of human pituitary adenomas in vitro.

The effects of testosterone (T), dihydrotestosterone (DHT) and methyltrienolone (R 1881) on cell proliferation of eight human pituitary tumors in culture wre assessed by [3H]thymidine incorporation and compared to those of progesterone (Pg) and 17 beta-estradiol. Receptors for androgens (AR), estrogens (ER) and progesterone (PgR) were characterized. AR had a significant inhibitory effect on all AR-positive tumors, whatever their hormonal content. Inhibitory effects of either T and DHT < R1881 < Pg were observed in tumors co-expressing AR and PgR. The inhibitory effect of R 1881 on a PgR-positive/AR-negative tumor suggested that R 1881 action was partially PgR-mediated. The effects of either T or the nonaromatizable DHT and R 1881 were unrelated to ER expression. We conclude that AR can modulate the growth of human pituitary tumors through direct receptor-mediated intracellular pathways which may be common to various pituitary cell types.

Adenoma↗

PubMed2005

Aromatase inhibitors: cellular and molecular effects.

Marked cellular and molecular changes may occur in breast cancers following treatment of postmenopausal breast cancer patients with aromatase inhibitors. Neoadjuvant protocols, in which treatment is given with the primary tumour still within the breast, are particularly illuminating. In Edinburgh, we have shown that 3 months treatment with either anastrozole, exemestane or letrozole produces pathological responses in the majority of oestrogen receptor (ER)-rich tumours (39/59) as manifested by reduced cellularity/increased fibrosis. Changes in histological grading may also take place, most notably a reduction in mitotic figures. This probably reflects an influence on proliferation as most tumours (82%) show a marked decrease in the proliferation marker, Ki67. These effects are generally more dramatic than seen with tamoxifen given in the same setting. Differences between aromatase inhibitors and tamoxifen are also apparent in changes in steroid hormone expression. Thus, immuno-staining for progesterone receptor (PgR) is reduced in almost all cases by aromatase inhibitors, becoming undetectable in many. This contrasts with effects of tamoxifen in which the most common change on PgR is to increase expression. Changes in proliferation occur rapidly following the onset of exposure to aromatase inhibitors. Thus, neoadjuvant studies with letrozole in which tumour was sampled before and after 14 days and 3 months treatment show that decreased expression of Ki67 occur at 14 days and, in many cases, the effect is greater at 14 days than 3 months. These early changes precede evidence of clinical response but do not predict for it. However, this study design has allowed RNA analysis of sequential biopsies taken during the neoadjuvant therapy. Based on clustering techniques, it has been possible to subdivide tumours into groups showing distinct patterns of molecular changes. These changes in tumour gene expression may allow definition of tumour cohorts with differing sensitivity to aromatase inhibitors and permit early recognition of response and resistance.

Anastrozole↗

PubMedDate not supplied

Effects of short-term tamoxifen administration in patients with invasive cervical carcinoma.

Cervical cancer is not considered a hormone-responsive tumor in spite of the presence of estrogen receptors (ER) and progesterone receptors (PgR) in some of them. Endocrine treatments have not achieved clinical responses, however, tamoxifen has been reported to induce PgR and to inhibit cell growth of many cervical carcinoma cell lines. In this study we investigated whether tamoxifen administration affects the histopathological characteristics of cervical cancer and the expression of ER, PgR, HER-2/neu and p53 protein. Nineteen patients with invasive cervical cancer free of previous treatments were studied. The triphenylethylene antiestrogen tamoxifen was given orally during 10 days (20 or 40 mg/day). Pre- and post-tamoxifen biopsies were evaluated using slides stained with hematoxylin and eosin and immunostained (ER, PgR, HER-2/neu, p53, PCNA, keratin, heat shock protein 27,000 daltons). Estrogen receptors were present in 37% and PgR in 16% of the biopsies from untreated patients. Only one case that was PgR-negative before tamoxifen administration showed weak PgR-positivity following antiestrogen administration. No obvious changes were observed in ER, HER-2/neu and p53 proteins. A statistically significant decrease in the number of mitotic figures was obtained in 16% (3/19) of the post-tamoxifen biopsies and two of them showed higher differentiation. The results showed that tamoxifen did not induce changes in estrogen-regulated proteins in cervical cancer. However, the data showed that certain cervical carcinomas had changes in their proliferation and differentiation levels following tamoxifen administration. These findings suggest that tamoxifen may affect some cervical cancer tissues by a hormone-independent mechanism(s).

Administration, Oral↗