[Expression of tumor necrosis factor-alpha (TNF-alpha) on peritoneal fluid mononuclear cells in women with endometriosis]. / Ekspresja receptorów dla czynnika martwicy guza-alpha (TNF-alpha) na jednojadrzastych komórkach immunokompetentnych plynu otrzewnowego u kobiet z endometrioza.

OBJECTIVES: Tumor necrosis factor-alpha (TNF-alpha) plays a key role in the processes underlying the development of pelvic endometriosis. TNF-alpha acts on target cells via two receptors: TNFR1(p55) and TNFR2(p75). Depending on cell type and its activation state, ligand binding to TNF-alpha may induce activation and proliferation of the cells or promote apoptosis. The aim of our study has been to evaluate the expression of TNFR1 and TNFR2 on peritoneal fluid macrophages and T lymphocytes derived from women with endometriosis. MATERIAL AND METHODS: The study group consisted of 22 patients with endometriosis (stage I and II rAFS). 14 patients with benign, non-inflammatory ovarian tumors composed the reference group. Mononuclear cells have been isolated from peritoneal fluid, obtained during laparoscopy. The expression of TNFR1 and TNFR2 proteins has been evaluated by means of flow cytometry, using monoclonal antibodies against CD120a, CD120b, CD3 and CD14. RESULTS: The percentage of peritoneal fluid macrophages revealing the expression of TNFR1 and TNFR2 proteins has been higher in patients with endometriosis, in comparison with control group (22.6+/-5.3% vs. 6.8+/-1,8%; p=0.03 and 29.3+/-2.3% vs. 8.8+/-1.8%; p=0.01, respectively). The percentage of T lymphocytes with the expression of TNFR1 and TNFR2 has been similar in endometriosis and control group. CONCLUSION: Higher percentage of peritoneal fluid macrophages expressing TNFR1 and TNFR2 proteins in endometriosis suggests dependence of these cells on TNF-alpha stimulation. Changes in TNF receptors distribution on PF macrophages, but not lymphocyte, may play its role in the pathogenesis of endometriosis.

Changing trends in the surgical treatment of female stress urinary incontinence--twenty two years observation.

OBJECTIVES: The aim of this study was to analyze the changing trends in surgical treatment of female urinary incontinence (UI). MATERIAL AND METHODS: Medical records of all women admitted to II Department of Gynecology from 1985 to 2006 were analyzed in order to find out how the female SUI treatment changed over these years. RESULTS: During analyzed time 36819 patients were hospitalized in our Department and 77.6% (28568) of them were operated because of various indications. The number of SUI surgeries among all hospitalized women steadily rose from 1.93% in 1985 to 10.96% in 2006 reaching maximum in 2005 (13.73%). Clinical effectiveness of SUI surgeries markedly improved from 35% for anterior colporrhaphy to almost 90 % for suburethral slings. CONCLUSIONS: Introduction into clinical practice modern suburethral slings improved clinical efficacy of SUI treatment. The percentage of women admitted and treated surgically because of SUI steadily increased over the last years.

Lack of correlation between leptin receptor expression and PI3-K/Akt signaling pathway proteins immunostaining in endometrioid-type endometrial carcinomas.

A number of studies published recently focused on the putative role of leptin in the pathogenesis of various primary human malignancies. Current study was aimed at investigating ObR, PI3-kinase, phospho-Akt kinase and PTEN proteins expression in forty-five primary human endometrioid-type endometrial carcinomas (EC). ObR immunostaining was detected in 21 of 45 (47%) ECs, presented in almost 60% of well- and moderately-differentiated tumors compared to only 17% of poorly-differentiated neoplasms (P<0.05). Semi-quantitative histological score (H-score) ObR values were inversely correlated with patients' body mass index (R=-0.35; P=0.019). ObR expression was significantly higher in normal weight compared to overweight and obese patients (P=0.024). All slides displayed intense PI3-kinase immunoreactivity, whereas phospho-Akt kinase expression was reported in 96% (43 out of 45) cases. Fifteen (33%) ECs were negative for PTEN expression, nine (20%) showed heterogeneous immunostaining pattern, whereas 21 (47%) were PTEN-positive. There was a trend towards a higher phospho-Akt kinase intensity immunostaining in PTEN-negative compared to PTEN-positive cases, but the difference was not significant. There was no significant association between each PI3-K/Akt signaling pathway proteins immunostaining in endometrioid-type ECs. In conclusion, ObR expression is associated with histological grading and the weight of women affected by EC. The components of PI3-K/Akt kinase signaling pathway are expressed in most of the primary endometrioid-type endometrial neoplasms.

CYP1A1 alleles in female genital cancers in the Polish population.

OBJECTIVE: Cytochrome P4501A1 (CYP1A1) plays an important role in the bioactivation processes that transform aromatic hydrocarbons into ultimate carcinogens. Genetically determined differences in activity of this enzyme could modulate individual susceptibility to develop cancers. The role of CYP1A1 in metabolic pathway of estrogens suggests an influence on carcinogenic events in genital tissues. The aim of our study was to elucidate the possible role of CYP1A1 alleles in the pathogenesis of endometrial and ovarian cancers. STUDY DESIGN: We have compared CYP1A1 genotype frequency between genital (endometrial and ovarian) cancer groups and 212 healthy women. Cancer patients were stratified using FIGO classification and diagnoses were confirmed histopathologically. The analysis of CYP1A1 genotypes was performed using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) assay. RESULTS: We have observed higher frequency of heterozygotic genotypes containing mutation m4 (CYP1A1*1/*4) in cancer groups (5.1% in ovarian and 5.6% in endometrial cancer versus 1.9% in controls). CONCLUSION: The higher frequency of mutated CYP1A1*4 allele connected with lower frequency of CYP1A1*2A and CYP1A1*2B in endometrial and ovarian cancer groups indicates that differences in the metabolic activity of CYP1A1 could play a significant role in the pathogenesis of genital cancers.

Expression of TGF-beta type I and II receptors in normal and cancerous human endometrium.

Transforming growth factor-beta (TGF-beta) belongs to a superfamily of structurally related polypeptides involved in various biological processes, including cell growth, proliferation and differentiation, angiogenesis, apoptosis, and extracellular matrix remodeling. We tried to define the different expression patterns of the TGF-beta receptors by investigating the female reproductive organs during the menstrual cycle and endometrial tumorigenesis, because their role in these processes is still unclear. In this study, we examined the expression of the TGF-beta type I and type II receptors in normal (n=13) and carcinomatous (n=42) endometrial tissue specimens using reverse transcriptase polymerase chain reaction and immunological (Western blot and enzyme linked immunosorbent assay) methods. Two uncommon female genital tract tumors, rhabdomyosarcoma of the uterine cervix and uterine carcinosarcoma, were also included. There were no significant differences between normal and cancerous endometrial tissues regarding the TGF-beta receptors mRNA levels. However, we observed a markedly low TGF-beta type I receptor protein level (P<0.028; Mann-Whitney-U test), while the malignant endometrium showed a significantly higher TGF-beta type II receptor protein level (P<0.007; Mann-Whitney-U test) than the normal endometrium. Moreover, significantly elevated TGF-beta receptor type II protein level was noted when depth of myometrial invasion of endometrial carcinomas was considered (P<0.05; Mann-Whitney-U test). In contrast to uterine carcinosarcoma, in which no detectable mRNA for TGF-beta type II receptor was found, we noted expression of both TGF-beta receptors in rhabdomyosarcoma of the uterine cervix. However, neither rhabdomyosarcoma of the uterine cervix nor uterine carcinosarcoma displayed TGFbetaRI and TGFbetaRII protein expression. This observation corroborates the complexity of the deregulation of TGF-beta receptor expression in human endometrial cancer.

Loss of heterozygosity of the retinoblastoma gene is correlated with the altered pRb expression in human endometrial cancer.

The retinoblastoma (Rb) gene was the first tumor suppressor gene to be discovered; however, data on the influence of Rb inactivation on endometrial carcinogenesis are scarce. We investigated 46 paired primary human endometrial carcinomas and normal tissues to assess the frequency of loss of heterozygosity (LOH) in Rb and 20 tumor pairs to detect the frequency of p53 LOH. Moreover, expression of the retinoblastoma protein (pRb) was assessed immunohistochemically. Of 44 informative cases 8 showed loss of one allele in at least one Rb marker; Rb LOH frequency thus reached 18%. Two omental metastases of endometrial origin showed a heterogeneity pattern similar to that of the primary tumors. We did not find a significant correlation between Rb LOH and patient age, clinical stage, histological grade or muscle invasion of the tumor. Nevertheless, Rb LOH was demonstrated at early (stage I, 5/27, 18%) and advanced (stages II-IV; 3/9, 33%) clinical stages of the neoplasm, suggesting that LOH at the Rb locus occurs before the clonal expansion of the tumor. There was a significant correlation between Rb LOH and weak/absent pRb expression. We noted a single case of p53 LOH at intron 1, but no tumor showed both alterations simultaneously. Our data suggest that LOH at the Rb locus plays a role in the oncogenesis of a subset of uterine neoplasms and corresponds with the altered expression of the pRb.

Clinicoprognostic significance of pRb1 pathway alterations in uterine endometrial adenocarcinoma.

Components of the pRb1 pathway play a pivotal role in regulating the G1/S transition in the cell cycle. This study investigated the association between pRb1-cyclin D1-cdk4-p16INK4A pathway alterations and the clinical and prognostic utility for women affected by primary uterine endometrial adenocarcinoma (EC). The study population consisted of 50 cases of EC patients who were investigated for RB1 and CDKN2A (alias p16INK4A) gene alterations, as well as for the expression pattern of pathway proteins. Altogether, pRb1 pathway alterations were noted in 54% (27 of 50) of ECs, and more frequently in advanced-stage uterine carcinomas (P=0.024, Fisher exact test). Loss of heterozygosity abnormalities in RB1 and CKDN2A coexisted with altered cyclin D1-cdk4 complex immunoreactivity only in 2 patients, both less than 50 years of age. With respect to pRb1 pathway alterations, however, the recurrence rate was not significantly different (P=0.477; log-rank test). Our results suggest that the progression of uterine endometrial adenocarcinoma is generally accompanied by increased frequency of pRb1 pathway alterations. Alterations of the retinoblastoma pathway may not be necessarily associated with the recurrence of EC.

Estrogen receptor alpha and beta expression in uterine leiomyomas from premenopausal women.

OBJECTIVE: To measure messenger RNA levels of estrogen receptor (ER) alpha and beta in uterine leiomyomas, normal myometrium, and endometrium. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Seventeen premenopausal women who underwent surgery due to symptomatic uterine leiomyomas. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Quantitative RT-PCR was used for evaluation of ERalpha and ERbeta expression. Results were normalized to total cellular DNA. RESULT(S): Expression of ERalpha and ERbeta did not differ between leiomyomas and myometrium; however, in both tissues, expression of ERalpha was significantly higher than that of ERbeta. Estrogen receptor-alpha expression in endometrium was lower than in leiomyomas and myometrium. In leiomyomas and endometrium, correlations between expression of ERalpha and ERbeta were found. CONCLUSION(S): Uterine leiomyomas, myometrium, and endometrium display distinct patterns of ER expression.

BAT-26 microsatellite instability does not correlate with the loss of hMLH1 and hMSH2 protein expression in sporadic endometrial cancers.

Microsatellite instability (MSI) is detected in about 20-25% of endometrial cancers (ECs). Incidence of this alteration correlates with lack of expression of certain mismatch repair genes such as hMLH1 and hMSH2. Although assessment of several markers has been proposed for identification of microsatellite unstable tumours, BAT-26, a mononucleotide microsatellite repeat, has been shown to be highly efficient when used as a single marker. The aim of the study was to evaluate instability within BAT-26 and expression of hMLH1 and hMSH2 proteins in sporadic endometrial cancer as well as to correlate these findings with histopathologic and clinical characteristics of tumours. Samples of 88 (74 endometrioid and 14 non-endometrioid) ECs were investigated for instability within BAT-26 by means of PCR and expression of hMLH1 and hMSH2 proteins using immunohistochemistry. BAT-26 MIS was discovered in 23.9% of endometrial cancers. Incidence of MSI did not correlated with grade, stage or depth of invasion. BAT-26 MSI was more frequent in non-endometrioid compared to endometrioid tumours (35.7% vs. 21.6%, respectively), but the difference was not statistically significant. Lack of hMLH1 and hMSH2 protein expression was detected in 21.6 and 15.9% of ECs, respectively, and did not correlate with clinicopathologic features of tumours. Loss of both hMLH1 and hMSH2 protein expression was similar in BAT-26 stable and unstable cancers. All cases of non-endometrioid tumours with BAT-26 MSI were positive for hMLH1. We can conclude that BAT-26 used alone may not be a reliable marker for identification of sporadic ECs with microsatellite instability induced by deficient expression of hMLH1 and hMSH2.

Expression and intracellular localization of Smad proteins in human endometrial cancer.

The aim of our study was to examine expression of Smad proteins i.e., Smad2, Smad3 and Smad4 both as mRNA and protein as well as their intracellular localization in normal (n=13) and neoplastic (n=42) endometrial tissue specimens using RT-PCR and immunological techniques i.e., Western blot and ELISA. Two uncommon female genital tract tumours, rhabdomyosarcoma of uterine of the cervix and uterine carcinosarcoma were also included. No statistically significant differences were found in the mRNA level of the examined Smad proteins between normal and tumour tissue specimens. Smad2 and Smad3 mRNAs were detected both in uterine carcinosarcoma and rhabdomyosarcoma of the uterine cervix. However, significantly lower Smad2 and Smad4 mRNA level was noted when the depth of myometrial invasion was considered (p<0.05). In endometrial cancer as compared to normal endometrium significantly higher levels of Smad2 and Smad3 proteins, both in cytoplasmic (p=0.002; p=0.0001) and nuclear (p=0.016; p=0.0004) fractions were observed. Both in uterine carcinosarcoma and rhabdomyosarcoma of the uterine cervix Smad2, Smad3 and Smad4 proteins were not detected. Moreover, significantly elevated Smad4 protein level in cytoplasmic fraction was stated when tumour grade and depth of myometrial invasion was undertaken (p<0.05). When intracellular distribution of Smads was considered differences between cytoplasmic and nuclear localization in normal and carcinomatous endometrium was stated. In endometrial cancer decreased number of cases with Smad3 and increased number of cases with Smad4 located in nuclear fraction was found. In conclusion, the disturbances in Smad protein expression and/or differences in their intracellular distribution suggest, that TGF-beta signaling pathway via Smads may be deregulated in endometrial carcinomas.

Global DNA methylation in relation to hMLH1 and hMSH2 protein immunoreactivity in sporadic human endometrial carcinomas.

Overall DNA methylation status was studied in a group of 28 sporadic human endometrial carcinomas (ECs) using the [32P]-postlabeling technique. Moreover, expression of the DNA mismatch repair proteins (hMLH1 and hMSH2) was investigated in ECs using immunohistochemistry. Mean 5-methyldeoxycytosine (m5dC) content in the studied group was 3.48+/-0.37% (range, 2.89-4.12%). The mean m5dC scores were significantly different between early (3.35+/-0.33%) and advanced (3.66+/-0.36%) endometrial neoplasms (chi2-test; p=0.03). There was a markedly increased overall DNA methylation with the degree of histological differentiation and with the infiltration of the myometrium (p<0.05). Loss of hMLH1 and hMSH2 expression was reported in 7 (25%) and 5 (18%) tumors, respectively, but the immunoreactivity did not correlate with the known clinicopathological variables of cancer. In addition, no obvious correlation was found between global m5dC content and the lack of hMLH1 and hMSH2 protein expression in human uterine tumors (p=0.97 and p=0.19 for hMLH1 and hMSH2, respectively; Spearman's rank correlation test). Our results clearly show that alterations in global DNA methylation may influence tumor progression, but they are not directly associated with the inactivation of the mismatch-repair machinery in sporadic human ECs.

Human cultured skin fibroblasts express estrogen receptor alpha and beta.

Human skin fibroblasts may be the target cells for estrogens. The aim of present study was to confirm the presence of both isoforms of estrogen receptors (ER) in these cells. Experiments were carried out in primary cultures of human skin fibroblasts. ER-alpha and ER-beta mRNAs were measured by quantitative assays based on reverse transcription (RT) of the mRNA and polymerase chain reaction (PCR) amplification of the cDNA. To determine which of the ER isoforms were present and their intracellular locations immunohistochemical staining was performed. MCF-7 culture was a positive control for the immunostaining. The distribution immunostaining of ER-beta protein differed from that of ER-alpha in skin fibroblasts. ER-alpha was detected in both the cytosolic and nuclear compartments of fibroblasts. ER-beta was weakly detectable and was found predominantly in the nuclear compartment. Using the RT-PCR technique mRNA of both ERs was successfully detected in the skin fibroblast cultures with predominantly higher mean level of ER-beta mRNA expression than ER-alpha mRNA. In human culture skin fibroblasts ER-beta co-expresses with ER-alpha. The dominant expression of ER-beta in cultured female skin fibroblasts suggests that ER-beta may play a dominant role in collaboration with ER-alpha in the regulation of estrogen action in skin.

Sialosyl-Tn expression in normal and pathological conditions of human endometrium. An immunohistochemical study.

To assess the clinico-prognostic relevance of the cell surface carbohydrate glycoprotein in normal and pathological conditions of human endometrium, Sialosyl-Tn (STn) antigen was immunohistochemically studied in normal (n = 10), hyperplastic (n = 18), and neoplastic (n = 60) endometrial lesions. There was no STn antigen reactivity in the proliferative endometrial slides, while weak staining was observed in all secretory endometria. STn expression was noted in 8/18 (44%) hyperplastic endometrial cases and in 40/60 (67%) endometrial carcinomas. Positive staining was observed throughout the cytoplasm of the glandular cancer cells, at the cell membranes, and in an intraluminar mucus. This antigen was mostly expressed heterogeneously as far as the distribution of positive cells is concerned. There was a statistically significant association between STn expression and the histological grading of cancer (p = 0.019). Advanced clinical stage (III-IV; p = 0.014) and infiltration of the myometrial wall (more than 1/2 of the myometrial wall; p = 0.004), but no STn immunoreactivity, were reported to be independent prognostic variables during follow-up. Our study shows that a) STn is not constantly expressed during the menstrual cycle, and is increased at the secretory phase of the cycle; b) Sialosyl-Tn reactivity decreases with the degree of tumor differentiation, but there was no relationship with other clinicopathological variables of cancer; c) this cell surface carbohydrate glycoprotein does not appear to predict the outcome of endometrial cancer patients.

Is diminished pubocervical fascia collagen content a risk factor for failure of surgical management of genuine stress urinary incontinence in women?

OBJECTIVE: The assessment of relationship between pubocervical collagen content and clinical results of surgical treatment of genuine stress urinary incontinence (GSUI) in women. METHODS: Twenty-four women treated for genuine stress urinary incontinence were included into the study. All women underwent the same surgical procedure. The samples of pubocervical fascia were taken at the time of surgery. The contents of acid soluble, pepsin soluble, insoluble fraction of collagen, total collagen and collagen crosslinks were measured. The study of pubocervical fascia collagen metabolism included also estimation of collagenase activity. At follow-up done 5 years following surgery, 20 patients reported symptoms of GSUI (study group). Four women were still without symptoms of urine leakage (control group). RESULTS: The biochemical parameters of pubocervical fascia did not show, statistically significant differences between compared groups. CONCLUSION: The pubocervical fascia collagen metabolism does not have impact on the results of anti-incontinence surgery.

Serum concentrations of markers of type I collagen metabolism in women taking monophasic oral contraceptives.

OBJECTIVES: To investigate serum concentrations of the carboxy-terminal propeptide of type I procollagen (PICP) and cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), reflecting the rate of synthesis and degradation of the parent collagen respectively, in women using monophasic oral contraceptives. STUDY DESIGN: PICP and ICTP were estimated in 60 women taking 20 micrograms of ethinyl estradiol (EE) + 150 micrograms of desogestrel (DSG) or 30 micrograms of EE + 150 micrograms DSG over six months. RESULTS: Mean PICP concentration decreased in women receiving 20 micrograms of EE + 150 infinity g of DSG after three cycles of administration. However, after six months this value returned to a level comparable to the initial one. In women taking 30 micrograms of EE + 150 micrograms of DSG the mean concentrations of PICP did not change significantly throughout the period studied. None of the oral contraceptives noticeably influenced the concentrations of ICTP. CONCLUSION: Investigated oral contraceptives do not significantly affect the metabolism of type I collagen, however a transient decrease in its biosynthesis may be expected during the use of formulations containing 20 micrograms of EE.

[TVT procedure--the critical analysis of clinical effectiveness and complications among first 100 cases]. / Operacja TVT--analiza skutecznosci oraz powiklan pierwszych 100 operacji.

RATIONALE: Since its clinical debut in 1996 TVT procedure has been offering an excellent clinical tool both for patients and surgeons to treat SUI suffering women. Since the learning curve is an important factor influencing the rate of surgical complications as well as the clinical outcome of any new surgical technique we decided to analyse the first 100 cases of SUI women treated with TVT technique. AIM OF THE STUDY: To analyse clinical effectiveness and complications among first 100 consecutive cases of TVT procedures. MATERIAL AND METHODS: One hundred women aged from 30 to 89 years (old mean 55.6) were hospitalised in our Department from September 1999 to November 2000 because of SUI as confirmed by the complete urogynecologic assessment including history and physical examinations, catheterised residual volume determination, and multichannel urodynamic testing. TVT procedure was performed as originally described by Ulmsten et al. except the fact that 43 operations were performed not under local but epidural anesthesia. For 80 patients TVT was offered as the primary surgery for SUI treatment whereas for 14 it was the second and for 6 the third or more attempt. RESULTS: Operation was performed without any technical difficulties in all cases (mean time 25 min). Bladder injury (treated by 1 or 2 days catheterization) occurred in 9 cases, urinary retention in 13 (in 6 cases after 10-14 days tape was cut). Urinary tract infections occurred in 4 women despite intraoperative 2.0 g i.v. piperacillin prophylactics and fosfomycin trometamol 3.0 g p.o. in first postoperative day. Subsequent urge incontinence developed in 4 patients. Clinical efficacy based on medical history, cough test and Gaudenz questionnaire was 95% (observation period 3 to 16 months, mean 8 months). CONCLUSIONS: In our opinion TVT procedure is an operation of choice to treat SUI in women regardless of their age because of its excellent clinical effectiveness accompanied by its technical simplicity, reproducibility and low percentage of serious complications. Previous urogenital surgery is a risk factor for bladder perforation during TVT procedure.

Expression of the cell-cycle regulatory proteins (pRb, cyclin D1, p16INK4A and cdk4) in human endometrial cancer: correlation with clinicopathological features.

INTRODUCTION: Derailments of the control mechanisms in the G1/S phase of the cell cycle play a fundamental role in the initiation and progression of cancer. However, only a few reports have addressed the issue of simultaneously occurring abnormalities of Rb-pathway components in malignant endometrial tumors. METHODS: Currently, we assessed the expression of cell-cycle regulatory proteins (pRb, cyclin D1, p16(INK4A) and cdk4) in 48 sporadic endometrial cancers, and investigated these tumors for a possible relationship between aberrant protein staining and clinicopathological variables of cancer and RB-LOH. RESULTS: There was abnormal pRb, cyclin D1, p16(INK4A) and cdk4 immunoreactivity in 2%, 50%, 6% and 25% of cases, respectively. Altogether, 33 of 48 (69%) endometrial malignant tumors showed abnormal expression of at least one Rb-pathway protein immunohistochemically. However, there was significant correlation neither between the cell-cycle regulators nor between the frequency of pRb, p16(INK4A) and cyclin D1 abnormalities and clinicopathological variables of cancer, but a significant correlation did exist between cdk4 staining and the clinical stage of disease ( P<0.05, Fisher's exact test). Moreover, an inverse relationship was also demonstrated between cdk4 expression and patient age ( r=-0.367; P=0.01). However, none of the cell-cycle regulatory proteins, except for pRb, was related to loss of heterozygosity at locus 13q14. CONCLUSION: As a conclusion, derailments of the Rb-pathway components, cyclin D1 and cdk4 in particular, seems to participate in the endometrial cancer development in humans. Overexpression of cdk4 was related to the progression of neoplastic disease and corresponds with age of onset, suggesting a major role of altered cdk4 immunoreactivity in the progression of endometrial cancer.

TGF-beta signaling is disrupted in endometrioid-type endometrial carcinomas.

OBJECTIVE: Previous studies have demonstrated deregulation of the expression and changes in the intracellular distribution of TGF-beta pathway components in human endometrial cancer (EC). The aim of this study was to assess the relationship between the expression of TGF-beta cascade components, including TGF-beta receptor type I (TGF beta RI) and type II (TGF beta RII), SMAD2, SMAD3, SMAD4, and clinicopathological features--tumor grade, FIGO classification, and depth of myometrial invasion--of type I (endometrioid-type) ECs to give some insight into the role of TGF-beta cascade components in endometrial tumorigenesis. METHODS: The expression of TGF beta RI, TGF beta RII, SMAD2, SMAD3, and SMAD4 was evaluated both at the mRNA and protein level using reverse transcription polymerase chain reaction (RT-PCR) and ELISA, respectively. RESULTS: Infiltrating endometrial carcinomas (less and more than half of the myometrial wall thickness) express significantly higher TGF beta RII protein level compared with non-infiltrating tumors (P = 0.04 and P = 0.01, respectively). Decreased level of SMAD2 and SMAD4 mRNAs was observed in the uterine tumors infiltrating less and more than half of the myometrial wall (P = 0.03 and P = 0.02, respectively) compared with noninfiltrating ECs. Significantly higher SMAD4 protein level in the cytoplasmic fraction of ECs was found when tumor grade and depth of myometrial invasion were considered (P < 0.05). Generally, tumor progression was associated with a decreased number of cases characterized by the presence of SMADs in the nuclear fraction only. CONCLUSION: Our data suggest that disturbances of the TGF beta RII and SMAD4 expression as well as localization of SMADs may be important to the infiltration of the myometrial wall by the type I endometrial carcinomas.

A randomized comparison between monofilament and multifilament tapes for stress incontinence surgery.

Our objective was to compare monofilament and multifilament tapes positioned without tension at the midurethra for postoperative complications and cure rate. One hundred patients with stress urinary incontinence were randomly allocated into two study groups. Using identical surgical methodology, 50 patients had a monofilament tape inserted at the midurethra using the TVT delivery instrument, and another 50 a multifilament tape using the IVS delivery instrument. The only significant difference between the groups was in the incidence of postoperative urinary retention ( p=0.023). Ten patients from the monofilament group required longer than normal ('normal' means to the morning of the next day) catheterization, in contrast to only two from the multifilament group. The clinical efficacy of both procedures was equally high. Conclusions were that both tapes appear to be equally effective in the surgical treatment of SUI. The higher incidence of postoperative urinary retention in the monofilament group was most likely caused by the elastic feature of this tape.

Evaluation of mRNA expression of estrogen receptor beta and its isoforms in human normal and neoplastic endometrium.

Endometrial cancer is well known to be estrogen-dependent. Two estrogen receptor types, ERalpha and ERbeta, are major mediators of a diversity of biologic functions of estrogen and play an important role in estrogen-dependent tissues and cancers. Cloning of ERbeta was followed by the discovery of a variety of its isoforms. Using real-time RT-PCR, the relative expression levels of ERbeta1, ERbeta2 (ERbetacx), ERbeta3, ERbeta4 and ERbeta5 were studied. We observed coexpression of ERbeta isoforms in the endometrium and upregulation of the ERbeta5 transcript in malignant endometrium. We also observed downregulation of ERbeta2Delta5 transcript in neoplastic endometrium, using a semiquantitative method. Our results suggest that analyzing the changes in ERbeta and its isoforms may be important in the diagnosis, prognosis and treatment of endometrial cancer.