Biomedical subjects

L Pylkkänen

Publications and source records attributed to L Pylkkänen.

At least 19 recordsLinked to original sources

PubMed2006

Service screening mammography reduces breast cancer mortality among elderly women in Turku.

OBJECTIVES: The aim of this study was to assess the effects of service screening mammography on breast carcinoma incidence and refined mortality among women aged 55-69 at entry in three cities employing different screening policies. METHODS: Since 1987, the city of Turku, Finland, has provided service screening mammography for women aged 55-69 at entry (in 1987), and Tampere provided screening for women aged 55-59 at entry, whereas Helsinki did not screen any of these age groups. The incidence of breast carcinoma during the screening period 1987-97 in women born in 1918-32 (1918-22, 1923-27, 1928-32) was compared with incidence during the pre-screening period 1976-86 in women born in 1907-21 (1907-11, 1912-16, 1917-21) in each city. The follow-up for mortality was four years longer. RESULTS: Breast carcinoma incidence was 31-38% higher in the screening period in all three cities irrespective of screening. In breast carcinoma mortality, no significant changes were seen in Helsinki or Tampere. In Turku, a 36% mortality reduction (relative risk [RR] 0.64; 95% confidence interval [CI] 0.47-0.88; P=0.007) in the whole study population and a 47% reduction in women aged 65-69 at entry (RR 0.53; 95% CI 0.28-0.99; P=0.047) were seen. CONCLUSIONS: The incidence of breast carcinoma increased in all study cities irrespective of screening. The comprehensive screening programme in Turku including women aged 55-69 at entry was associated with a significant reduction in breast carcinoma mortality. The pronounced decrease in mortality in the oldest age group (65-69 years at entry) also indicated that women of this age group greatly benefit from mammography screening.

Age Factors↗

PubMed2002

Prevention of bone loss by clodronate in early postmenopausal women with vertebral osteopenia: a dose-finding study.

This double-masked, placebo-controlled study was undertaken to determine the efficacy and safety of oral clodronate in the prevention of bone loss in early postmenopausal women with vertebral osteopenia. Altogether 610 women with a mean age of 53 years were recruited for the study. They were 1-5 years postmenopausal and their lumbar spine bone mineral density (BMD) was at least 1 standard deviation below the mean of premenopausal women ( T-score < or =-1). The subjects were randomized into five study groups to receive either placebo, clodronate 65 mg, 400 mg or 800 mg daily, or intermittent clodronate in 3 month cycles with 400 mg daily for 15 days followed with no treatment for 75 days for 3 years. One hundred and eighty-seven of 509 women who completed the primary study continued in the extension study of 2 years in which previous placebo users were switched to clodronate 800 mg daily, while previous users of 400 mg or 800 mg of clodronate used either placebo or 800 mg of clodronate daily. In the primary study clodronate was administered in the evening, and in the extension 1 h before breakfast on an empty stomach. In the primary study mean changes in lumbar spine BMD were -3.4% in the placebo group and +0.4% in 800 mg clodronate group [difference between groups at 3 years 3.8% (95% CI 2.7% to 4.9%, p<0.0001)], and in the trochanter area BMD -1.1% in the placebo group, and + 0.4% in the 800 mg clodronate group [difference between groups at 3 years 1.5% (95% CI 0.05% to 2.9%)]. During the extension study mean changes in lumbar spine BMD were +1.5% in the clodronate group and -0.2 % in the placebo group [difference between groups 1.7% (CI 0.4% to 3.0%, p = 0.010)] and in trochanter BMD were +2.5% in the clodronate group and no change in the placebo group [difference between groups 2.1% (CI 0.3% to 3.9%, p = 0.007)]. No statistically significant differences between the placebo and 800 mg clodronate groups were found in the femoral neck BMD. In the primary study the urinary excretion of type I collagen aminoterminal telopeptide (NTX) decreased by 44% ( p<0.0001 compared with placebo) and that of deoxypyridinoline by 18% ( p<0.0001) in the clodronate 800 mg group. In the extension study urinary NTX decreased by 51% ( p<0.0001) in those who were switched to 800 mg of clodronate and increased by 67% ( p<0.0001) in those who stopped using that dose. There was no difference in the frequency of gastrointestinal complaints between clodronate- and placebo-treated patients in the primary study, but they were more common among women who received clodronate in the extension phase. Clodronate in daily doses of 400-800 mg caused a slight elevation of aminotransferase levels, usually within the reference range. In bone biopsies no defect in mineralization was found. In conclusion, clodronate in a daily dose of 800 mg prevents early postmenopausal bone loss at the sites of the skeleton in which cancellous bone predominates. It effectively reduces bone resorption and bone turnover rate. Antifracture efficacy of clodronate remains to be established by prospective, placebo-controlled trials.

Absorptiometry, Photon↗

PubMed2002

The absolute bioavailability of clodronate from two different oral doses.

Clodronate (disodium clodronate tetrahydrate) is a bisphosphonate used in the treatment of hypercalcemia and osteolysis due to malignancy. Like all bisphosphonates, clodronate has low and variable oral bioavailability. The purpose of this study was to examine the absolute bioavailability of clodronate from two different oral doses. Thirty-one healthy young volunteers participated in this open, randomized, three-period, single-dose, cross-over study. The absolute bioavailability was calculated from the area under the serum clodronate-time curve in 48 h (AUC(0-48 h)) after administration of 800 or 1600 mg (Bonefos 400 mg capsules) of oral clodronate, or 30 mg (Bonefos 60 mg/mL infusion concentrate) of intravenous clodronate. The maximum concentration of clodronate in serum (C(max)), the time to maximum concentration (t(max)), the elimination half-life (t(1/2)), and the cumulative amount of clodronate excreted into urine in 48 h (Ae(0-48 h)) were also determined. The geometric mean of the absolute bioavailability of 800 mg of clodronate was 1.9% and that of 1600 mg 2.1%. The difference in the absolute bioavailability of these two doses was statistically nonsignificant. All treatments were well tolerated, and the AE profiles were similar in the different treatment groups. There were no serious adverse events during the study.

Administration, Oral↗

PubMed2001

Omission of histologic grading from clinical decision making may result in overuse of adjuvant therapies in breast cancer: results from a nationwide study.

PURPOSE: To investigate the influence of routinely performed histologic grading on breast cancer outcome prediction and patient selection for adjuvant therapy. PATIENTS AND METHODS: The analysis is based on a cohort of 2,842 women diagnosed with breast cancer and comprising 91% of all breast cancers diagnosed in five defined geographical regions in Finland in 1991 through 1992. Data on clinicopathologic factors and follow-up were collected from hospital case records and national registries. Histologic grade assessed at diagnosis and other clinicopathologic data were available for 1,554 operable unilateral invasive carcinomas. The relative value of grade with respect to competing prognostic factors was estimated with the Cox proportional hazards model and logistic regression. Interactions and nonlinearity of factors were accounted for by using an artificial neural network. RESULTS: Histologic grade was correlated strongly with survival in the entire series and in all subgroups studied. Women with well-differentiated node-negative cancer had a 97% 5-year distant disease-free survival rate as compared with 78% for women with poorly differentiated cancer. Grade was an independent prognostic factor in multivariate models and increased the predictive accuracy of a neural network model. Inclusion of grade data in a Cox multivariate model based on tumor size and hormone receptor status in node-negative cancer increased the proportion of patients with 5% or less risk for distant recurrence at 5 years from 15% to 54%. CONCLUSION: Even when assessed by pathologists who have no special training in breast cancer pathology, histologic grade has substantial and independent prognostic value in breast cancer. Omission of grading from clinical decision making may result in considerable overuse of adjuvant therapies.

Adult↗

PubMed2001

Clinical and biochemical response to single infusion of clodronate in active rheumatoid arthritis--a double blind placebo controlled study.

OBJECTIVE: To investigate the efficacy and tolerability of intravenous clodronate in patients with rheumatoid arthritis (RA). TREATMENT AND METHODS: Twenty-six patients with active RA were randomly allocated to receive either a single iv. infusion of placebo or 600 mg clodronate. Efficacy and safety were assessed weekly during the following three weeks by clinical and laboratory evaluations. RESULTS: Serum osteocalcin and carboxyterminal propeptide of type I procollagen (markers of bone metabolism) were significantly decreased in the clodronate group at the end of the study, whereas the indices of disease activity including number of swollen joints, number of tender joints, patient's and doctor's estimation of condition (visual analogue scale), erythrocyte sedimentation rate and serum C-reactive protein level were not affected by clodronate treatment. No serious adverse effects were observed. CONCLUSIONS: A single infusion of clodronate in patients with RA was safe and caused a decline in the markers of bone metabolism, but this short-term treatment did not suppress disease activity. Results from recent clinical and preclinical studies, however, suggest that the anti-inflammatory efficacy of clodronate requires liposome encapsulation.

Adult↗

PubMed2000

Timing of food intake has a marked effect on the bioavailability of clodronate.

Because of the low and variable bioavailability of bisphosphonates and the huge effect of food on their gastrointestinal absorption, it is of utmost importance to know the optimal timing of drug intake in relation to food intake. We investigated the effect of time on the bioavailability of clodronate when the drug was administered 2, 1, or 0.5 h before breakfast, with breakfast, or 2 h after breakfast (in the middle of a 4-h fast). The study was conducted as a single-center, open, balanced, randomized, crossover pharmacokinetic study in 31 healthy subjects aged 21 to 34 years. The volunteers participated in five different sessions with 800 mg of oral clodronate, and these sessions were separated by washout phases, each for at least 1 week. The primary pharmacokinetic variables were the area under the serum concentration time curve in 24 h (AUC(0-24)) for clodronate and the maximal concentration of clodronate in serum (C(max)). Clodronate was absorbed rather similarly when taken in the morning on an empty stomach 2, 1, or 0.5 h before breakfast, but because the best absorption occurred (as expected) when the drug was taken 2 h before breakfast, this scheme served as the reference treatment. As evaluated by area under the serum concentration time curves, the dose-breakfast interval of 1 h scarcely reduced absorption from the reference treatment level (relative absorption 91%, p = 1.0). Compared with the reference treatment, clodronate was absorbed with 69% efficacy (p = 0.65) when breakfast followed only 0.5 h later. The dose-breakfast intervals of 0.5 and 1 h did not differ significantly from each other (p = 0.85). Absorption was, however, only 34% (p < 0.0001) of the optimum when the drug was taken 2 h after breakfast, and only 10% of optimal when clodronate was taken with breakfast (p < 0.0001). In conclusion, it can be recommended to take Bonefos capsules in the morning on an empty stomach at least 0.5 h before breakfast.

Adult↗

PubMed1999

Late mortality from pT1N0M0 breast carcinoma.

BACKGROUND: pT1N0M0 breast carcinoma (< or = 2 cm in greatest dimension, lymph node negative) is associated with generally favorable 5-year and 10-year survival, but to the authors' knowledge there are few data available regarding the long term outcome of these patients. METHODS: The authors identified women with breast carcinoma diagnosed between 1945-1984 in a geographically defined urban population using the files of the Finnish Cancer Registry and local hospital records (n = 1495). The clinical and autopsy records and histologic slides were reviewed. The series contained 265 patients with unilateral pT1N0M0 breast carcinoma treated with mastectomy and axillary lymph node dissection without adjuvant systemic therapy and who were followed for 10-44 years (median, 17 years) after the initial diagnosis or until death. RESULTS: The last death from pT1N0M0 breast carcinoma occurred 23 years after the initial diagnosis. The 20-year overall survival rate was 54% (95% confidence interval [95% CI], 48-60%) and the survival rate when corrected for intercurrent deaths was 81% (95% CI, 75-87%). The 20-year survival rate when corrected for intercurrent deaths was 92% (95% CI, 86-98%) in patients with T1a-b disease (primary tumor < or = 10 mm), but was only 75% (95% CI, 64-86%) in patients with pTc disease (range, 11-20 mm). None of the patients with well differentiated (World Health Organization Grade 1) pTa-b tumors died of breast carcinoma (n = 48) whereas the 20-year survival rate when corrected for intercurrent deaths was 81% (95% CI, 67-95%) in patients with Grade 2-3, pT1a-b tumors (P = 0.002). CONCLUSIONS: Patients with well differentiated pT1a-b tumors form a subgroup with excellent long term prognosis, but a significant proportion of women with either moderately or poorly differentiated pT1a-b tumors or pT1c tumors ultimately die of the disease.

Adult↗

PubMed1999

Artificial neural networks applied to survival prediction in breast cancer.

In this study, we evaluated the accuracy of a neural network in predicting 5-, 10- and 15-year breast-cancer-specific survival. A series of 951 breast cancer patients was divided into a training set of 651 and a validation set of 300 patients. Eight variables were entered as input to the network: tumor size, axillary nodal status, histological type, mitotic count, nuclear pleomorphism, tubule formation, tumor necrosis and age. The area under the ROC curve (AUC) was used as a measure of accuracy of the prediction models in generating survival estimates for the patients in the independent validation set. The AUC values of the neural network models for 5-, 10- and 15-year breast-cancer-specific survival were 0.909, 0.886 and 0.883, respectively. The corresponding AUC values for logistic regression were 0.897, 0.862 and 0.858. Axillary lymph node status (N0 vs. N+) predicted 5-year survival with a specificity of 71% and a sensitivity of 77%. The sensitivity of the neural network model was 91% at this specificity level. The rate of false predictions at 5 years was 82/300 for nodal status and 40/300 for the neural network. When nodal status was excluded from the neural network model, the rate of false predictions increased only to 49/300 (AUC 0. 877). An artificial neural network is very accurate in the 5-, 10- and 15-year breast-cancer-specific survival prediction. The consistently high accuracy over time and the good predictive performance of a network trained without information on nodal status demonstrate that neural networks can be important tools for cancer survival prediction.

Adult↗

PubMed1998

Long-term survival in node-positive breast cancer treated by locoregional therapy alone.

To investigate the long-term survival rate of node-positive (pN+) breast cancer treated by locoregional therapy alone, we made an attempt to identify all such patients followed up for at least 15 years after treatment in a defined geographical area (city of Turku, Southwestern Finland) and time period (1945-79) using the files of the local hospitals and the Finnish Cancer Registry. The clinical and autopsy records and histological slides of 1172 women diagnosed with breast cancer in the city were reviewed. From this cohort we identified 339 women with unilateral node-positive breast cancer treated with locoregional therapy without systemic adjuvant therapy. The relative survival rate of the cohort compared with the general female population matched for age and year of follow-up was calculated. The 15- and 30-year survival rates corrected for known intercurrent deaths were 26% (95% CI, 21-31%) and 21% (16-26%) respectively, and the relative survival rates 23% and 21% respectively. None of the patients with pN2 disease survived for 15 years, whereas the 30-year corrected survival rate in pN1 disease was 24% (18-30%). Women with pT1N1M0 cancer had as high as 59% (43-75%) 15-year survival rate corrected for intercurrent deaths. A trend for improving survival was found by the decade of diagnosis. The results indicate that a considerable proportion of women with pN1 breast carcinoma treated with locoregional therapy alone become 30-year survivors and are probably cured. Adequate locoregional treatment is mandatory in the care of node-positive breast cancer.

Adult↗

PubMed1997

No evidence of microsatellite instability but frequent loss of heterozygosity in primary resected lung cancer.

We examined microsatellite instability and loss of heterozygosity (LOH) in primary lung tumors from 93 cancer patients, using 16 microsatellite markers. The cases studied included 87 non-small-cell lung cancers (NSCLC) and six small-cell lung cancers (SCLC). All the patients except two were current or former smokers. The microsatellite markers were all dinucleotide repeat sequences from chromosomal locations 1p, 3p, 5q, 8p, 9p, 10p, 11p, 13q, and 17q. None of the tumors showed microsatellite instability (0/93). In NSCLC, 28% (24/87) of the cases showed LOH in at least one locus, whereas, in SCLC, 67% (4/6) had allelic losses. The frequency of LOH differed between the various cell types of NSCLC. The highest frequency was seen in large cell carcinoma (3/6, 50%) followed by squamous cell carcinoma (16/43, 37%) and adenocarcinoma (5/35, 14%). The most common site of LOH was 3p, where markers D3S1284, D3S659, D3S1289, D3S966, D3S647, and D3S1038 were studied. LOH, studied with 9p markers (D9S126, D9S171, D9S162), was less common. The present results, together with earlier reports, suggest that smoking-related primary lung cancers seldom show microsatellite instability but are characterized by frequent LOH.

Adult↗

PubMed1997

Treatment results of osteogenic sarcoma. An evaluation of 36 patients treated during 30-year period in south-western Finland.

Histological re-evaluation revealed 36 osteogenic sarcoma (OS) patients for analysis in South-Western Finland treated between 1958 and 1987. In 21 cases (58%) the tumour was located in the knee region. The mean age at diagnosis was 28 years (range: 5-62 years) and the follow-up time of the patients was at least 5 years or until death. In 29 patients without metastases at the time of diagnosis, the extent of the primary tumour was T2 in 37% and T3 in 63% of the patients. There were no differences regarding the extent of the primary tumour, delay of the diagnosis, mean age of the patients, or duration of the symptoms while comparing the three decades of the study. Before the 1970s the treatment consisted of surgery with or without radiotherapy in most cases. Since the 1970s the combination of surgical treatment (amputation or wide excision) and adjuvant chemotherapy was the most common treatment modality. Since the late 1970s limb-salvage surgery has been applied in selected cases, and it seems to be justified. None of the patients treated before 1970 survived for 5 years. The 5- and 10-year survival of all 36 patients was 44.4% and 33.6%, respectively. In non-metastatic patients both the 5- and 10-year disease-free survival was 46.7%. A certain group exhibiting a good prognosis was found; the 10-year survival of the 10 patients with OS in extremities, treated with combined chemotherapy and surgery, was 70%. The median survival time was significantly longer for the patients with an intracompartmental tumour extent of T2 (112 months) compared with an extracompartmental extent of T3 (23 months), and for the patients with the primary tumour in the knee region (112 months) compared with other locations (18 months). The long-term survival of the OS patients has improved concomitantly with the multimodality of the treatment.

Adolescent↗

PubMed1997

Invasive lobular carcinoma of the breast has better short- and long-term survival than invasive ductal carcinoma.

The outcome and prognostic factors of 217 women with invasive lobular carcinoma (ILC) and those of 1121 women with invasive ductal carcinoma (IDC) of the breast were compared. The patients were followed up for 10-43 years. Women with ILC had axillary nodal metastases less frequently than those with IDC (43% vs 53%, P = 0.02), although there was no difference in the primary tumour size between the groups. ILCs were more frequently of low grade, had lower mitotic counts and had less tumour necrosis. Furthermore, ILCs had lower S-phase fractions and were more often DNA diploid in flow cytometric analysis than IDCs (P < 0.0001 for all comparisons). The 5- and 30-year corrected survival rates of women with ILC were 78% and 50%, respectively, compared with 63% and 37% for women with IDC (P = 0.001). Small pT1NOMO ILCs (n = 41) had 100% 10-year and 83% 20-year corrected survival rates. In a multivariate analysis, a large primary tumour size, the presence of axillary nodal metastases, a high mitotic count and the presence of tumour necrosis all had an independent prognostic value in ILC. We conclude that ILC is associated with better survival than IDC.

Adult↗

PubMed1996

Animal models for the preneoplastic lesions of the prostate.

OBJECTIVES: Reliable and adequate animal models are required, not only for investigation of etiology, pathogenesis, and treatment of prostate cancer, but also for chemoprevention of prostatic carcinogenesis. METHODS: Animal models for the study of premalignant changes in the prostate are reviewed in the paper, with specific reference to the neonatally estrogenized mouse model. RESULTS: Neonatal treatment of newborn Han:NMRI mice with synthetic non-steroidal estrogen, diethylstilbestrol (DES; 2 micrograms/pup on days 1-3 after birth) promoted hyperplastic and dysplastic changes in the periurethral region of the prostate at the age of 9-18 months. Dietary soy partially inhibited the development of prostatic dysplasia in these neonatally estrogenized animals, which may be due to phytoestrogens contained in soy-rich food. CONCLUSION: Prostatic cancer and its possible precursors develop spontaneously, or can be induced by different chemical and hormonal manipulations in certain animal species and strains. Neonatal estrogenization of the mouse results in prostatic dysplasia, which can be partially prevented by dietary soy. There are morphological similarities between human prostatic intraepithelial neoplasia (PIN) and dysplastic changes in rodent prostates, but more data is needed before these dysplastic lesions can be considered equivalent to human PIN.

Animals↗

PubMed1995

p53 protein detected by immunohistochemistry as a prognostic factor in patients with epithelial ovarian carcinoma.

BACKGROUND: The clinical significance of p53 suppressor gene nucleoprotein immunostaining in ovarian epithelial cancer has not been determined. METHODS: p53 protein expression was studied by immunohistochemistry from paraffin embedded tissue in a series of 136 patients with malignant ovarian epithelial tumors. The median follow-up time of the patients still alive was 10 years. RESULTS: Sixty (44%) carcinomas stained clearly positive for p53 protein. Positive staining for p53 protein was associated with the serous histologic type (P = 0.0006), a higher than the median S-phase fraction size determined by DNA flow cytometry (P = 0.02), and poor histologic grade of differentiation (P = 0.04), but not with the International Federation of Gynecology and Obstetrics (FIGO) stage, age at diagnosis, or DNA ploidy. Cancers with positive staining had only 17% 5-year and 9% 15-year survival rates compared with 42% 5-year and 36% 15-year survival rates corrected for intercurrent deaths among the rest of patients (P = 0.002). In a multivariate analysis, positive p53 staining was associated with poor survival (relative risk of death, 1.8, 95% confidence interval [CI], 1.2-2.9) together with less than radical surgery (nonradical vs. radical: RR, 5.5; 95% CI, 2.2-13.6), and advanced FIGO stage (RR, 1.4; 95% CI, 1.0-2.0). CONCLUSION: Although p53 protein immunostaining is associated with several other prognostic factors in epithelial ovarian cancer, it may also have independent prognostic value in this disease.

Adult↗

PubMed1994

Close linkage to chromosome 3p and conservation of ancestral founding haplotype in hereditary nonpolyposis colorectal cancer families.

A susceptibility to hereditary nonpolyposis colorectal cancer (HNPCC) was recently shown to be due to mutations in the MSH2 gene on chromosome 2p. A second susceptibility locus has been mapped to chromosome 3p in two families. The present report describes the results of a genetic study of Finnish HNPCC kindreds. Of 18 apparently unrelated families living in different parts of the country, 11 could be genealogically traced to a common ancestry dating at least 13 generations back in a small geographic area. Linkage studies were possible in 9 families, revealing conclusive or probable linkage to markers on 3p in 8. Five of these were among those having shared ancestry. The location of the gene was refined by a linkage study comprising 12 marker loci. By analysis of recombinations in such families, the HNPCC locus could be assigned to the 1-centimorgan interval between marker loci D3S1561 and D3S1298. A haplotype encompassing 10 centimorgans around the HNPCC locus was conserved in five of the pedigrees with shared ancestry and present in 2 further families in which linkage analysis was not possible. Our results suggest the presence of a widespread single ancestral founding mutation. Moreover, the map position of the 3p gene for HNPCC susceptibility was greatly refined.

Adenoma↗

PubMed1994

p53 protein, PCNA staining, and DNA content in follicular neoplasms of the thyroid gland.

Forty-nine follicular adenomas and 11 follicular carcinomas of the thyroid were investigated by immunohistochemistry for the expression of p53 protein and proliferating cell nuclear antigen (PCNA). The DNA ploidy and the S-phase fraction (SPF) of the neoplasms were analysed by flow cytometry. Twelve adenomas (24 per cent) and six carcinomas (55 per cent) were DNA non-diploid (P = 0.07). The carcinomas had a higher proliferation rate than the adenomas when assessed either by SPF size (median 9.9 per cent vs. 2.9 per cent, P = 0.0003) or by PCNA staining intensity (P < 0.0001). Some scattered nuclei in two (4 per cent) adenomas and in three (27 per cent) carcinomas stained positively for p53 (P = 0.04). The two adenomas with positive staining for p53 were subserially sectioned, but no signs of invasion were found; both patients are alive and well 6 and 7 years after surgery. One of the two adenomas showing positive p53 nuclear staining was DNA aneuploid, and both were positive in PCNA staining, but their SPFs were low (2.1 and 3.3 per cent). We conclude that p53 protein expression is not confined to follicular carcinomas; scattered p53-positive cells may also be present in histologically and clinically benign follicular adenomas. Because both follicular adenomas and carcinomas may be DNA aneuploid and their SPF and PCNA staining distributions overlap, the distinction between follicular adenoma and carcinoma should still be based on histological criteria.

Adenocarcinoma, Follicular↗

PubMed1994

Developmental estrogenization and prostatic neoplasia.

The association of estrogens with benign prostatic hyperplasia and prostatic cancer has been widely studied, but no conclusive evidence exists for a role of estrogens in prostatic disease. This paper reviews the literature and describes studies which have sought to show a correlation of estrogens and alterations in the prostates of humans and experimental animal models. Using the developmentally estrogenized mouse model, we propose an alternative role for estrogens as a predisposing factor for prostatic diseases: estrogen exposure during development may initiate cellular changes in the prostate which would require estrogens and/or androgens later in life for promotion to hyperplasia or neoplasia. Thus, the critical time for estrogen action would be during the development of the prostatic tissue. We further suggest that estrogen-sensitive cells may remain in the prostate and be more responsive to estrogens later in life or less responsive to the normal controlling mechanisms of prostatic growth.

Adult↗

PubMed1994

Immunohistochemical localization of estrogen-specific 17 beta-hydroxysteroid oxidoreductase in the human and mouse prostate.

The estrogen-specific 17 beta-hydroxysteroid oxidoreductase (17 beta-HSOR) enzyme protein was stained immunohistochemically in the newborn and adult human prostate as well as in the mouse prostate. In the newborn human prostate, ductal and urethral epithelia were faintly stained, whereas in the adult human prostate, intense staining for 17 beta-HSOR enzyme antigen could be detected in the epithelium of the collecting ducts and urethral epithelium as well as in the epithelium of the intraprostatic vas deferens and seminal vesicle epithelium. Immunostaining was weak in the prostatic tissues of both newborn and adult prostate. No positive cells were found in stroma. The activity of NADPH-dependent 3H-estrone reductase was detectable in cell-free homogenates prepared from human prostatic tissues. The activities showed a good correlation with immunocytochemical findings. In the mouse, neonatal estrogenization resulted in intensively stained epithelium of the collecting ducts at the age of 14 days. Moreover, when adult control and neonatally estrogenized mice were implanted with 17 beta-estradiol, the metaplastic epithelium of the periurethral collecting ducts of neonatally estrogenized mice was intensively stained with 17 beta-HSOR. These findings suggest that metaplastic epithelium rises from 17 beta-HSOR-positive cells. The similar distributions of 17 beta-HSOR-positive cells confirm the concept of homology in the posterior estrogen-responsive periurethral region (containing the periurethral ducts and periurethral glands) of the mouse and humans. Our findings further suggest that the 17 beta-HSOR-positive cells may have the same origin and hormonal control in both species.

Adult↗