Biomedical subjects

B Têtu

Publications and source records attributed to B Têtu.

At least 37 records · Page 2Linked to original sources

PubMed1999

Immunocytochemical localization of type 5 17beta-hydroxysteroid dehydrogenase in human reproductive tissues.

17beta-hydroxysteroid dehydrogenase (17beta-HSD) controls the last step in the formation of all androgens and all estrogens. At least six 17beta-HSD isoenzymes have been identified. The recently cloned Type 5 17beta-HSD transforms 4-dione into testosterone. To gain a better understanding of the role of this enzyme in reproductive tissues, we immunocytochemically localized the enzyme in human male and female reproductive organs. In the ovary of adult premenopausal women (25-40 years of age), immunostaining was found in corpus luteum cells. In the uterus, staining was detected only in the epithelial cells of the endometrium. Immunolabeling was also detected in the mammary gland, a positive reaction being detected in epithelial cells of acini and intralobular ducts as well as in the surrounding stromal cells. In the testis, strong staining was seen in the Leydig cells, and a weak but specific reaction was occasionally detected in Sertoli and germ cells. In the prostate, specific labeling was observed in alveoli and stromal fibroblasts. In alveoli, all the basal cells were generally labeled, whereas the luminal cells exhibited variations in immunoreactivity. In all the reproductive organs examined, specific staining was routinely detected in the walls of blood vessels, including the endothelial cells. These results indicate a cell-specific localization of Type 5 17beta-HSD in the different human reproductive organs, thus suggesting new mechanisms of local androgen and estrogen formation that may play an important physiological role.

17-Hydroxysteroid Dehydrogenases↗

PubMed1999

Predictive value of cell cycle markers p53, MDM2, p21, and Ki-67 in superficial bladder tumor recurrence.

The aim of the study was to determine whether the expression of the cell cycle markers p53, MDM2, p21, and Ki-67 was predictive of superficial bladder cancer recurrence and to compare the relative predictive power for tumor recurrence of a cell cycle index based on the number of abnormally expressed cell cycle markers with a clinicopathological index based on primary clinical tumor characteristics. The expression of p53, MDM2, and p21 proteins and the value of the Ki-67 index were analyzed for 244 patients. One hundred ninety-four lesions were determined to be superficial papillary tumors (pTa), whereas 50 tumors invaded the lamina propria (pT1). Tumor grade was noted low (grade 1) in 83 cases and high (grades 2-3) in 161 cases. An avidin-biotin peroxidase method was performed using monoclonal antibodies against p53, MDM2, p21, and Ki-67 antigens after antigen retrieval treatment of formalin-fixed specimens. The cell cycle marker index was created using the number of abnormally expressed cell cycle markers according to the following cutoff points: p53 (>5%), MDM2 (>20%), p21 (<5%), and Ki-67 (>10%). The clinicopathological index was created using the following adverse tumor characteristics: grades G2-G3, stage pT1, multifocality, and diameter of tumors > 3 cm. Cox regression models were used to calculate the relative risks and their 95% confidence intervals associated with disease recurrence for the clinicopathological index and the cell cycle marker index. The chi2 test was performed to describe the correlation between the Ki-67 index and p53, MDM2, and p21 protein expression. Kaplan-Meier survival curves were generated to demonstrate the disease-free survival according to these two prognostic indexes. The clinicopathological index was a strong, independent predictor of disease recurrence where tumors with three or four adverse tumor characteristics at initial resection had over four times the risk of recurrence than tumors with no risk factors (P for trend = 0.0001). A strong correlation was observed between the Ki-67 index >10% and both MDM2 and p21 proteins. MDM2 was overexpressed in 106 tumors (43%), and p53 was overexpressed in 47 (19%); Ki-67 was >10% in 171 cases (70%). Thirty-nine tumors (16%) were p21 negative. The risk of recurrence increased slightly with the number of abnormally expressed cell cycle markers, but when the clinicopathological index was taken into account in multivariate analysis, the cell cycle marker index was not predictive of disease recurrence (P for trend = 0.72). The cell cycle markers studied provided no added prognostic information on disease recurrence after initial resection of papillary superficial tumors when the clinicopathological parameters were taken into account.

Aged↗

PubMed1998

Cycling activity of benign prostatic epithelial cells during long-term androgen blockade: evidence for self-renewal of luminal cells.

Combined androgen blockade (CAB) therapy (LHRH agonist and flutamide) for 6 months leads to marked regressive changes of the prostate gland. This is associated with a reduction in the ratio of luminal to basal cells in the peripheral zone (PZ) in hyperplastic glands of the transitional zone (TZ). To examine the cycling activity of luminal and basal cells, double immunostaining was performed. For precise definition of basal cells, the basal cell-specific antibody 34 beta E12 was used, while cycling cells were identified by the MIB-1 antibody. In 6-month-treated specimens, the fraction of cycling luminal cells increased from 0.3 to 2.5 per cent in the PZ and from 0.2 to 3.9 per cent in the TZ. This was associated with an inversion of the ratio of MIB-1-labelled luminal to basal cells, with values of 5.7:1 (PZ) and 3.9:1 (TZ), compared with 1:4 (PZ) and 1:5 (TZ) in untreated specimens. The predominance continued for at least 11 years of CAB. The findings strongly suggest that luminal cells are capable of self-renewal under conditions of low androgen levels. The substantial decrease of prostatic volume on long-term CAB implies that cell loss outweighs cell proliferation.

Androgen Antagonists↗

PubMed1998

Prognostic significance of stromelysin 3, gelatinase A, and urokinase expression in breast cancer.

This study was aimed at testing the hypothesis that the expression of proteases essentially produced by reactive stromal cells (stromelysin-3 [ST3], gelatinase A [GELA], and urokinase [uPA]) is predictive of prognosis in patients with breast cancer. This was a study of patients with node-positive and node-negative breast cancer diagnosed from 1980 to 1986 and with an average of 10 years follow-up. ST3 (665 cases), GELA, and uPA (575 cases each) expression was obtained by in situ hybridization on formalin-fixed, paraffin-embedded material using mRNA antisense probes. ST3 was expressed by 86.6% of the cases; GELA, 77.7%; and uPA, 64.7%. A significant correlation (P < .05) was found between high (more than 10%) ST3 expression and a younger age, lymph node involvement, poor nuclear grade, ductal histology, aneuploidy, and HSP-27 expression. High GELA expression was significantly associated with c-erbB2, ductal histology, and HSP-27 expression. High uPA expression correlated with poor nuclear grade, ductal histology, lack of estrogen and progesterone receptors, and p53 protein accumulation. High level of expression of all three proteases correlated significantly with each other and with cathepsin D expression by reactive stromal cells. By univariate analysis, both ST3 and uPA expression significantly predicted a shorter recurrence-free survival (ST3, P = .0199; uPA, P = .0269). By multivariate analyses, the prognostic significance was lost, most particularly at longer term. This study adds support to the concept that protease expression by reactive stromal cells is related to cancer cell characteristics but that their contribution to cancer progression is marginal.

Adult↗

PubMed1998

The early clinical course of primary Ta and T1 bladder cancer: a proposed prognostic index.

OBJECTIVE: To develop a simple prognostic index for anticipating more precisely the early clinical course of primary superficial bladder cancer. PATIENTS AND METHODS: The prognostic value of patient and tumour characteristics was examined in 333 patients with primary Ta or T1 bladder cancer who participated in a multicentre prospective study already completed. Primary tumour multiplicity, a diameter of > 3 cm, stage T1, and grade 2 or 3 were independent predictors of earlier recurrence in a multivariate analysis. A simplified prognostic index consisted of the number of adverse tumour characteristics (ATCs) initially present. RESULTS: After a median follow-up of 35.3 months, the 60 patients free of ATCs (19%) had a recurrence-free probability at 12 and 24 months of 86% and 69%, respectively, and none experienced progression. Recurrence outcomes deteriorated consistently as the number of ATCs increased among the other three groups. In patients with 3-4 ATCs, the 12- and 24-month recurrence-free probability was as low as 30% and 19%, and recurrence and tumour rates were about 2.6 times higher than in patients free of ATCs; 7% of these patients experienced progression within 35 months of follow-up. CONCLUSION: A prognostic index based on the number of ATCs (primary tumour multiplicity, diameter > 3 cm, stage T1, and grade 2 or 3) is a strong indicator of the clinical course of superficial bladder cancer within 3 years of the first endoscopic resection. This proposal is suggested for discussion and for validation in future studies but if confirmed, this simple prognostic index may greatly help to identify indicators for adjuvant intravesical therapy and to determine the optimal periodicity of control cystoscopy regimens.

Adult↗

PubMed1998

p53 and c-erbB-2 as markers of resistance to adjuvant chemotherapy in breast cancer.

Recent literature suggests that c-erbB-2 and p53 alteration might be linked to drug resistance. This study investigates the relation of c-erbB-2 oncoprotein overexpression and p53 protein accumulation with prognosis in patients with node-positive breast cancer (NPBC) and assesses the modifying effect of these markers on response to short (1-10 courses) or prolonged (> 10 courses) adjuvant chemotherapy. This study is based on 458 patients with NPBC diagnosed from 1980 to 1986, with an average of 10 years of follow-up. Marker expression was evaluated by immunohistochemical analysis on formalin-fixed, paraffin-embedded material with antibodies to c-erbB-2 and p53. c-erbB-2 was expressed in 17.2% of the cases, and 19.1% of the tumors stained positively for p53. By multivariate analysis, women with prolonged adjuvant chemotherapy had better survival than those with a short course of chemotherapy among patients whose tumor lacked c-erbB-2 oncoprotein expression (P = .0245) or p53 protein accumulation (P = .0477). Prolonged chemotherapy, however, was associated with little or no change in survival among patients whose tumor expressed those markers. The present study adds support to the hypothesis linking c-erbB-2 and p53 expression to drug resistance.

Adult↗

PubMed1997

mdr1 mRNA expression by RT-PCR in patients with primary breast cancer submitted to neoadjuvant therapy.

mdr1 expression by reverse transcription and polymerase chain reaction (RT-PCR) has been compared to P-glycoprotein (Pgp) expression by immunohistochemistry (IHC) and correlated with clinical response to neoadjuvant therapy. RNA has been recovered from glass slide smears of fine-needle aspiration from 57 untreated primary breast cancers prior to neoadjuvant chemotherapy (33 cases), hormone therapy (23 cases), or both (1 case). Furthermore, mdr1 mRNA has been analyzed in 6 cases after 2 months of treatment. The neoadjuvant therapy consisted of 4 cycles of adriamycin and cyclophosphamide or tamoxifen. Of 57 tumor specimens, an interpretable result was obtained in 52 cases, indicating the feasibility of the analysis by RT-PCR with very small tumor specimens. The presence of mdr1 mRNA has been documented in 44/52 (84%) tumor samples with a spectrum of expression levels. The expression of mdr1 mRNA was compared with P-glycoprotein (Pgp) expression by IHC using JSB-1, 4E3, and C494 monoclonal antibodies in 48 of the 52 interpretable tumor samples. 12/48 (25%) expressed Pgp by IHC. All tumors expressing Pgp by IHC were also positive by RT-PCR. The results confirm the higher prevalence of mdr1 mRNA compared to the protein expression. However, mdr1 mRNA expression was found to correlate significantly with resistance to neoadjuvant hormone therapy only while Pgp expression detected by JSB-1 immunostaining only correlated with chemoresistance. The lack of convincing correlation with chemoresistance suggests that mRNA and Pgp may not be directly or solely responsible for clinical response to drugs. Further studies should focus on the post-translational modulation of P-glycoprotein and other mechanisms of drug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

Markers of radioresistance in squamous cell carcinomas of the head and neck: a clinicopathologic and immunohistochemical study.

PURPOSE: The lack of accurate criteria to predict the response to radiotherapy for individual patients with squamous cell carcinoma of the head and neck (HN-SCC) remains a major problem. The purpose of this study was to investigate the role of several biologic tumor markers to complement clinical prognostic factors in the assessment of response to radiotherapy in SCCs. PATIENTS AND METHODS: p53, ki-67, c-erb B-2, heat-shock protein-27 (HSP-27), and glutathione S transferase (GSTpi) were evaluated by immunohistochemistry on biopsies from 101 patients treated for head and neck cancer by radical radiotherapy. Expression of each marker was correlated with local control and survival using Kaplan-Meier curves. A Cox regression multivariate analysis was also performed that included all clinical and immunohistochemical variables. RESULTS: Expression of p53 and low cell proliferation allowed identification of patients whose tumors did not respond to radiation. Patients with p53-expressing tumors displayed a relative risk (RR) of 3.78 for not being controlled by radiotherapy compared with patients with p53-negative tumors. For tumors with a high growth fraction (ki-67 > 20%) the RR was 0.25 compared with tumors with a low growth fraction (ki-67 < 20%). When p53 expression and cell proliferation were considered simultaneously in a Cox model, the association with resistance to radiation was significant (P = .000004). The RR for resistance with one (p53 staining or ki-67 < 20%) or two (p53 staining and ki-67 < 20%) unfavorable markers was, respectively, 3.8 and 14.87. CONCLUSION: Patients whose tumor expressed p53 with low growth fraction (ki-67 < 20%) had a strong probability not to respond to radiation therapy. Similarly, absence of p53 expression with a high cell proliferation predicted an excellent outcome after radiotherapy even for patients with advanced disease. Prediction of the outcome of radiotherapy would eventually facilitate the early choice of an adequate treatment.

Adult↗

PubMed1997

Immunohistochemical study suggesting a complementary role of kallikreins hK2 and hK3 (prostate-specific antigen) in the functional analysis of human prostate tumors.

The development of monoclonal antibodies directed against prostatic kallikrein hK2 prompted us to evaluate its content, along with that of hK3 (prostate-specific antigen), in human prostate carcinoma. Seventy tumors categorized according to the M.D. Anderson Hospital classification (grade I to IV) were analyzed by immunohistochemistry. The staining intensity or the kallikrein content of benign prostatic hyperplasia glandular tissue (used as control) and of grade I tumors appeared similar. In grade II to IV tumors, histochemical data revealed highly variable hK2 or hK3 content in approximately 25% of tumors. Such patterns are consistent with a current observation related to heterogeneity of prostate tumors. In addition, a few tumors did not express hK3 (n = 3), hK2 (n = 3), or both (n = 3), indicating that some growth patterns of prostatic neoplasia are associated with a lack of secretion or storage of hK3 or hK2 for immunodetection. This statement also appears relevant to metastases. It was interesting to note that 4% of hK3-negative tumors had detectable hK2. Because of the importance of hK3 as a serum marker of prostate disorder, this study addresses for the first time the question of the relative importance of both hK3 and hK2 in the immunohistochemical diagnosis of prostatic tumors. We conclude that hK2 may add new information to prostate cancer diagnosis and characterization.

Carcinoma↗

PubMed1997

Diagnostic accuracy of urinary cytology, and deoxyribonucleic acid flow cytometry and cytology on bladder washings during followup for bladder tumors.

PURPOSE: We evaluated the diagnostic accuracy of cytology on urine and bladder washings, and deoxyribonucleic acid (DNA) flow cytometry on bladder washings compared to cystoscopy during followup for bladder tumors. MATERIALS AND METHODS: A cross-sectional analysis was performed on 166 patients with a history of bladder tumor for the initial visit when cytology and DNA flow cytometry results were available for urine and bladder washing samples. There were 114 bladder tumor events and 52 negative controls (normal cystoscopy). A prospective study was conducted among the 66 patients with no tumor detected by cystoscopy at the initial visit and for whom the 3 test results were available. The patients were followed from this visit until tumor recurrence or the end of the followup period. Cytological examination was considered positive only when interpreted as malignant. Suspicious examinations were considered negative for the purpose of our study. RESULTS: Sensitivity and specificity of urinary cytology were 59 and 85%, respectively. Sensitivity was increased to 66% using bladder washing cytology whereas specificity was moderately decreased to 83%. The sensitivity and specificity of DNA aneuploidy were 45 and 87%, respectively. Inclusion within the aneuploid category of hyperdiploid samples (defined as more than 7% of cells in the S + G2M phase) increased sensitivity to 77%, while specificity decreased to 42%. Kaplan-Meier analysis of tumor-free survival in patients initially free of bladder cancer at cystoscopy showed an inability of DNA flow cytometry to predict recurrence, whereas positive urine or bladder washing cytology predicted a shorter time to recurrence (log-rank test p <0.01). CONCLUSIONS: These results show that DNA flow cytometry and cytology on bladder washing samples add little information to that obtained from voided urine cytology.

Cross-Sectional Studies↗

PubMed1996

Androgen receptor modulation in benign human prostatic tissue and prostatic adenocarcinoma during neoadjuvant endocrine combination therapy.

Modulation of androgen receptor (AR) expression during neoadjuvant endocrine therapy in human prostates of patients with localized prostate cancer was investigated by immunohistochemistry. In 8 of 15 untreated prostatectomy specimens, the majority of prostatic glandular cells displayed nuclear immunostaining for AR, whereas only 1 of 26 pretreated cases displayed a similar glandular AR expression. Expression of AR in the prostatic stromal compartment of nontreated cases proved to be quite heterogeneous, since 4 of the 15 (27%) examined specimens did not show stromal AR expression. After preoperative neoadjuvant therapy, this value was 68%, although this difference did not reach statistical significance. Prostatectomy specimens of the treated patients contained carcinomas with a higher Gleason score than those of untreated patients. AR expression in carcinomas of treated patients was diminished (P= 0.05), which may be attributed to their relatively lower differentiation grade. The data strongly suggest that neoadjuvant hormone therapy reduces AR expression by nonneoplastic prostatic glandular cells and carcinoma cells by a selective, but incomplete, elimination of AR-positive cells.

Adenocarcinoma↗

PubMed1996

Vaginal radical hysterectomy versus abdominal radical hysterectomy in the treatment of early-stage cervical cancer.

The purpose of this study is to compare the safety, efficacy, and potential benefits of vaginal radical hysterectomy (VRH) versus abdominal radical hysterectomy (ARH) in the treatment of early-stage cervical cancer. We reviewed the charts of our first 52 patients with cervical cancer. We reviewed the charts of our first 52 patients with cervical cancer who underwent a laparoscopic pelvic lymphadenectomy (LPL), followed either by a VRH (Schauta) in 25 cases or ARH in 27 cases. For the 52 patients, the mean lymph nodes count obtained by LPL was 27 (range 8-59), and the only complication was an external iliac vein trauma requiring laparotomy. Both VRH and ARH groups were comparable in terms of age, weight, parity, stage, histology, and tumor volume. The mean blood loss was 400 cc for VRH vs 450 cc for ARH, operating time was 270 min vs 280 min, blood transfusion in 5 vs 4 women, and postoperative stay was 7 days for both groups. The only intraoperative complication in addition to the vein trauma was a cystotomy which occurred in 2 VRH patients. Febrile morbidity was noted in 4 VRH patients vs 9 ARH patients. There were one preperitoneal abscess and one hematoma in the VRH group vs 4 wound infections and 1 hematoma after ARH. Ileus occurred in 1 VRH vs 4 ARH patients. The current mean follow-up time is 27 months (8-52) and there has been one recurrence so far in the ARH group. Even though this is a retrospective study, our data indicate that VRH and ARH are comparable, except for the absence of an abdominal scar and less febrile morbidity with the vaginal approach. However, in our opinion, the main advantage in learning the Schauta operation is that the experience gained allows one to offer radical trachelectomy to selected young patients who wish to preserve their fertility.

Adult↗

PubMed1996

Prognostic significance of nuclear DNA content and S-phase fraction by flow cytometry in primary papillary superficial bladder cancer.

This study is aimed at determining the usefulness of nuclear DNA content and S-phase fraction (SPF) to predict tumor recurrence in papillary superficial bladder cancer. Tumor DNA content and SPF were measured by flow cytometry on formalin-fixed, paraffin-embedded tissue from 199 newly diagnosed pTa/pT1 transitional cell carcinomas of patients enrolled into a multicenter prospective study from 1990 to 1992. The follow-up extended up to March 1994, and, at last follow-up, 122 (61.3%) patients have experienced at least one recurrence. After exclusion of 34 cases, whose coefficient of variation exceeded 8%, 131 (79.4%) tumors were diploid, and 34 (20.6%) were aneuploid. There was no association between tumor DNA content and time to first recurrence. Diploid tumors with low SPF (< 11%) tended to have a longer recurrence-free survival (RFS) than those with high SPF, but this difference did not reach statistical significance (P = .2833). SPF in aneuploid tumors did not add any new information. Aneuploidy was associated with higher stage (P < .001), poorer grade (P < .002), multifocality (P = .028), Her-2/neu (P = .021), and p53 (P = .033) expression. High SPF correlated with higher stage (P = .066) and higher grade (P = .025). This study shows that DNA-ploidy and SPF measured on a single superficial bladder cancer specimen are not predictive of tumor recurrence. The frequent multifocality of the disease may explain, in part, these findings.

Adult↗

PubMed1996

Markers of chemoresistance in ovarian carcinomas: an immunohistochemical study of 86 cases.

Markers of chemoresistance have been rarely investigated in human ovarian cancer. This study evaluates the clinical value in ovarian cancer of metallothionein (MT), heat-shock protein-27 (HSP-27) and glutathione-S-transferase pi and alpha (GST pi, GST alpha), recognized for their relation with drug resistance in vitro. The expression of these markers was evaluated by immunohistochemistry on paraffin-embedded tumor specimens from 86 patients with ovarian carcinomas diagnosed between 1977 and 1990 who received chemotherapy. Response to chemotherapy was evaluated using well-defined criteria. Marker expression was evaluated on a section of the primary tumor (81 cases) and, when available, on a section of tumor following chemotherapy (48 cases). MT was expressed in 38.3% of primary tumors unexposed to chemotherapy, HSP-27 in 50.6%, GST pi in 37%, and GST alpha in 50.6%. The expression of all four markers did not help to predict chemoresistance. The concordance between marker expression by the tumor before and after chemotherapy was weak (concordance, 51.2%-70.7%). Immunostaining was not associated (p > 0.1) with any prognostic factor such as stage, residual tumor after surgery and grade. Ovarian cancer is a highly heterogeneous neoplasm and the expression of markers of chemoresistance reflects this heterogeneity. Our data suggest that chemoresistance is more likely multifactorial and confirms the complexity of the in vivo model.

Adult↗

PubMed1996

Androgen receptors in untreated and treated prostatic intraepithelial neoplasia.

OBJECTIVES: The effect of androgen deprivation therapy on the expression of androgen receptors (AR) and the proliferation-associated MIB-1 antigen in prostatic intraepithelial neoplasia (PIN) was investigated. METHODS: Immunohistochemistry was performed on tissue sections of prostatectomy specimens of patients with prostate cancer who either were not treated prior to surgery or received androgen blockade therapy for 3 months. Immunohistochemistry on slides, selected for the presence of PIN was performed with an AR-specific monoclonal antibody and MIB-1 using a microwave antigen-retrieval method. RESULTS: AR expression was present in a majority of cells in PIN of both untreated and treated prostatectomy specimens. In addition, a proportion of normal prostatic glandular cells retained AR expression. The basal cells in both untreated and treated PIN did not express AR. MIB-1-positive cells were identified in PIN of untreated and treated cases. CONCLUSIONS: PIN lesions that persist after 3 months of androgen deprivation therapy continue to express AR and may therefore retain the potential to expand after cessation of this therapy.

Androgen Antagonists↗

PubMed1996

[Prevention of second primary cancer with vitamin supplementation in patients treated for head and neck cancers].

Second primary cancers often occur in head and neck cancer patients successfully treated by radiation therapy. Experimental and epidemiological data suggest that these second primaries might be prevented by antioxidant vitamins, in particular beta-carotene and alpha-tocopherol. A randomized double-blind clinical trial is being conducted in Canada to determine whether vitamin supplementation with beta-carotene (30 mg/d) and alpha-tocopherol (400 IU/d) reduces the incidence of second primaries in head and neck cancer patients treated by radiation therapy.

Acetylcysteine↗

PubMed1996

[Incidence and risk factors of second primary cancers in patients treated for primary pharyngeal cancer].

About 13% of patients treated for a pharyngeal cancer suffer from a second primary cancer. Excessive consumptions of tobacco and/or alcohol are recognized as risk factors of second primary cancers in these patients. Epidemiologic studies suggest that antioxidant vitamins could have a protective effect on the occurrence of second primary cancers; however, this hypothesis should be confirmed by randomized clinical trials. A better knowledge of the risk factors of second primary cancers in patients with a pharyngeal cancer could help reducing the occurrence of second primary cancers and improving the follow-up of these patients.

Canada↗

PubMed1996

Elevated estrogen receptor expression in human prostatic stromal cells by androgen ablation therapy.

PURPOSE: The presence of estrogen receptors (ER) in human prostatic tissue is a longstanding, controversial issue. In a few experimental animal models androgen deprivation was shown to be associated with a spontaneous increased ER expression in prostatic tissue. We intended to study whether these observations also apply to human prostatic tissue. MATERIALS AND METHODS: Estrogen receptor expression by stromal and glandular cells was studied by immunohistochemistry in prostatectomy specimens of 21 patient with prostate cancer, treated for 3 months with a luteinizing hormone-releasing hormone (LHRH) agonist and flutamide. In addition 2 patients treated with estrogens were also examined. For comparison, ER expression was also studied in a series of 18 prostatectomy specimens of untreated patients. RESULTS: The specimens of patients treated with androgen blockade showed atrophic changes of the gland as well as basal cell hyperplasia, features characteristic for this therapy. Although stromal cells of prostatectomy specimens from untreated patients were largely ER negative, those of patients exposed to androgen ablation therapy or estrogen therapy had an intense nuclear ER expression in a great number of stromal cells around prostatic glands. Sporadic epithelial cells lining the glands displayed some nuclear ER expression. Prostatic glands from treated patients with basal cell hyperplasia lacked ER expression. In all treated and untreated cases the carcinoma cells were ER negative. CONCLUSIONS: Androgen deprivation leads to an upregulation of stromal ER expression in human prostate. Estrogen-induced morphological epithelial changes could be explained by a paracrine interaction between stromal and epithelial cells.

Androgen Antagonists↗