[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.

Leptin is not involved in the pathophysiology of endometriosis-related infertility.

OBJECTIVE: Changes in peritoneal fluid (PF) composition may affect fertilization as well as early embryonic development. Leptin, an adipocyte hormone, has been shown to act as a link between adipose tissue and the reproductive system. Therefore, we decided to assess peritoneal and serum leptin levels in infertile endometriotic patients. PATIENTS: Seventy-two women were studied, including 30 fertile and 18 infertile women with ovarian endometriotic cysts and, as a reference group, 24 patients with unexplained infertility. RESULTS: No significant difference in the peritoneal and leptin levels was found between the studied groups. Significantly higher PF leptin concentration was observed in patients with stages III and IV of endometriosis as compared to those with minimal stage of the disease. In fertile patients with endometriosis a positive correlation has been found between PF and serum leptin concentrations. CONCLUSIONS: No differences in peritoneal or serum leptin levels between infertile and fertile women with endometriosis suggest that this cytokine is not involved in pathophysiology of endometriosis-related infertility.

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.

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.

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.

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.

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.

Differential effects of estradiol, raloxifene and tamoxifen on estrogen receptor expression in cultured human skin fibroblasts.

The balance between ER-alpha and ER-beta in fibroblasts may be crucial in the physiological response to ligands. Up- or down-regulation of the ERs in response to different compounds could mediate the reversal of certain age-related changes in skin and connective tissue. The time-dependent effects of 17-beta estradiol, raloxifene and tamoxifen on ER-alpha and ER-beta mRNA expression in the skin fibroblast cultures were performed. Experiments were carried out in primary cultures of human skin fibroblasts obtained from postmenopausal women. The cells were cultured in medium containing: 2 micromol/l estradiol (E2), 4 micromol/l tamoxifen (Tx) or 4 micromol/l raloxifene (Rx) for 7, 24 and 32 h. 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. We suggest that ER-alpha and ER-beta are co-expressed in human postmenopausal skin fibroblast and documented that the level of mRNA expression of ERs in this tissue is estradiol, raloxifene or tamoxifen regulated as a mechanism to control the action of those ligands on the cell. On the basis of ER mRNA expression levels, fibroblast response to estradiol appears to be modulated by up-regulation of ER-beta rather than ER-alpha. Two of the examined SERMs appear to have different response to modulation of ERs: response of raloxifen is modulated by up-regulation of ER-beta, and no changes in expression of ER-alpha and tamoxifen response seem to be modulated by ER down-regulation in short-term or up-regulation during longer treatment.

The immunological profile of infertile women after repeated IVF failure (preliminary study).

OBJECTIVE: The aim of this preliminary study was to estimate the immunological profile of patients after repeated IVF failures. MATERIALS AND METHODS: Seventeen women after repeated IVF failure and 10 non-pregnant women with a history of successful IVF pregnancies were included in the study. We estimated the presence of the auto-antibodies, such as: antinuclear antibodies (ANA), antithyroid antibodies (ATA), antiphospolipid antibodies (APA), antismooth muscle antibodies (ASMA), and antisperm antibodies (ASA). Furthermore, we estimated the percentage of B-1 CD 19+5+ lymphocytes and NK cells using flow cytometry. RESULTS: In the group of patients after IVF failure the percentage of B-1 CD 19+5+ lymphocytes was higher than 1.5% and significantly higher when compared to controls. Three patients after IVF failure had elevated percentages of peripheral blood NK cells. Fourteen infertile patients after IVF failure (82.3%) had at least one abnormal result on autoimmune testing. One patient from the study group had no positive results of immunological tests. CONCLUSION: Our results suggest that immunological alterations may be involved in the etiopathogenesis of unexplained infertility. Furthermore, the results suggest that there is a need for immunological diagnostics in the group of patients with unexplained infertility A greater number of patients is needed for further investigations.

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.

Alterations of pRb1-cyclin D1-cdk4/6-p16(INK4A) pathway in endometrial carcinogenesis.

The retinoblastoma protein pathway (pRb1-cyclin D1-cdk4/6-p16(INK4A)) participates in the regulation of the cellular processes at the transition of G1/S phases of the cell-cycle. Derailments of this pathway, caused either by lack of pRb1 or p16(INK4A) expression or overexpression of cyclin D1 and/or cdk4/6, are implicated in the deregulation of the cell-cycle machinery, resulting in uncontrolled cell proliferation, tumor heterogeneity, invasion and metastasis. Several studies conducted so far have assessed the deregulation of the pRb1-pathway components in various human tumors and cell-lines, provided these pathway alterations play an obligatory role in tumorigenesis. This review briefly summarizes the current information on the pRb1-cyclin D1-cdk4/6-p16(INK4A) alterations in sporadic uterine cancer, placing emphasis on the influence on the dualistic model of endometrial carcinogenesis.

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.

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.

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.

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.

[Luteinizing hormone (LH) in hypergonadotropic hypogonadism]. / Hormon luteinizujacy (LH) w hypogonadyzmie hypergonadotropowym.

The serum LH concentration was analyzed in 47 patients of reproductive age with diagnosed hypergonadotropic hypogonadism based on clinical status, pituitary hormone and sex steroids levels, karyotype, ultrasound scan, CT scan, laparoscopy and ovarian biopsy. The following groups were categorized: 46XY, 45X0, premature ovarian failure, WHO III group and iatrogenic symptoms after surgery. The mean serum FSH level was similar in each study group. The serum LH concentration was the lowest in 45X0 group compared to the highest values in 46XY and surgically treated groups. The LH/FSH ratio was close to normal in 46XY and surgically treated groups. We conclude the syndrome should be recognized mainly on basis of FSH level since the LH level shows heterogenic fluctuations. The serum LH concentration is close to normal for physiological conditions (postcastrated menopause, male genotype) but significantly lower in ovarian disorders and gonadal dysgenesis.

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.

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.