Search

Background: Ovarian epithelial cancers are among the most lethal women's cancers. There is no doubt about the preventive role of oral contraceptive pills (OCPs) in development of ovarian cancers. But, there are limited numbers of studies to address the effect of these agents on the number of cortical inclusion cysts (CICs), their epithelial type and suppression of the metaplastic phenomenon by these pills. The aim of this study was to clarify the role of these agents in the prevention of these cyst formation and tubal metaplasia and also examine the mesenchymal-epithelial transition theory in this context by immunohistochemical methods., Methods: The representative section(s) of ovarian cortex from a total number of 201 consecutive total abdominal hysterectomy with bilateral or unilateral salpingo-oophorectomy specimens were examined for mean number of CICs and their epithelial type between two groups of the patients. Group A included the patients who were on oral contraceptive pills for more than 5 years. All of the subjects with other contraceptive methods or a history of less than 5 years contraceptive pills usage were stratified in group B. Sections from 20 cases in which more than five inclusion cysts were found, were selected for IHC staining with calretinine and PAX8 as markers for mesothelium and mullerian epithelium respectively., Results: The mean age of the patients was 51.67 years with no significant differences between two groups. The mean number of cysts were 1.27 and 3.23 in group A and B respectively (P =0.0001). Similarly the mean number of CICs, lined by tubal epithelium, was significantly different between two groups (0.65 vs 2.65, P =0.0001). In IHC staining 123 out of 150 CICs (82 %) were PAX+ while only 7 CICs (4.8 %) showed positive reaction for calretinin irrespective of type of epithelium., Conclusion: Our findings showed that the use of OCP for more than five years in women, significantly prevents development of cortical inclusion cysts in the ovaries which lined by tubal (PAX8 positive) type epithelium. These findings may explain the alternative mechanism of oral contraceptive pills or long time use of progesterone in suppression of tubal type overgrowth and subsequently prevention of ovarian epithelial cancers.

The importance of high-resolution mass spectrometry for the correct data interpretation of a direct tissue analysis is demonstrated with an example of its clinical application for an endometriosis study. Multivariate analysis of the data discovers lipid species differentially expressed in different tissues under investigation. High-resolution mass spectrometry allows unambiguous separation of peaks with close masses that correspond to proton and sodium adducts of phosphatidylcholines and to phosphatidylcholines differing in double bond number.

Cystic ovarian disease (COD) is one of the main causes of infertility in dairy cattle. It has been shown that intra-ovarian factors, such as members of the insulin-like growth factor (IGF) system, may contribute to follicular persistence. The bioavailability of IGF to initiate its response by binding to specific receptors (IGFRs) depends on interactions with related compounds, such as pregnancy-associated plasma protein A (PAPP-A). The aim of this study was to determine IGFR1 and PAPP-A expression both in follicles at different stages of development and in cysts, to evaluate the roles in the etiopathogenesis of COD in cattle. The mRNA expression of PAPP-A was higher in granulosa cells of large tertiary follicles than in cysts, whereas the protein PAPP-A present in the follicular fluid from these follicles showed no differences. Although no PAPP-A mRNA expression was detected in smaller tertiary follicles, in their follicular fluid, this protease was detected in lesser concentration than in cysts. The mRNA expression of IGFR1 was lower in granulosa cells from cystic follicles than in those from tertiary ones. However, the protein expression of this receptor presented the highest levels in cystic structures, probably to increase the possibility of IGF response. The data obtained would indicate that animals with COD have an altered regulation of the IGF system in the ovary, which could be involved in the pathogenesis of this disease in cattle., (© 2015 Blackwell Verlag GmbH.)

Hepatocyte nuclear factor-1β (HNF-1β) is a transcriptional factor that has an important role in endometriosis-ovarian clear cell carcinoma (OCCC) sequence by modulating cell kinetics and glucose metabolism. However, little is known about the detailed molecular mechanisms that govern its regulation and function. Herein, we focus on upstream and downstream regulatory factors of HNF-1β in OCCCs. In clinical samples, HNF-1β expression was positively correlated with the active form of NF-κB/p65 in OCCCs, and closely linked with a low nuclear grade and non-solid architecture. In cell lines, transfection of p65 resulted in increased HNF-1β mRNA and protein expression in TOV-21G cells (OCCC cell line with endogenous HNF-1β expression), in line with activation of the promoter, probably through interacting with the basic transcriptional machinery. Suppression of endogenous HNF-1β expression by siRNA increased apoptosis in TOV-21G cells, while treatment of Hec251 cells (endometrial carcinoma cell line with extremely low endogenous HNF-1β expression) stably overexpressing exogenous HNF-1β with doxorubicin abrogated apoptosis of the cells, along with increased ratio of bcl-2 relative to bax. Moreover, overexpression of HNF-1β led to upregulation of bcl-2 expression at the transcriptional level in TOV-21G cells, which provided evidence for a positive correlation between HNF-1β and bcl-2 expression in OCCCs. These data, therefore, suggest that association between HNF-1β and NF-κB signaling may participate in cell survival by alteration of apoptotic events, particularly in mitochondria-mediated pathways, through upregulation of bcl-2 expression in OCCCs.

Objective: The objective of this study was to compare the biochemical composition of follicular cysts, pre-ovulatory follicles and serum in sows., Material and Methods: The research involved multiparous sows (cysts-bearing sows, n = 21; non-cysts-bearing sows, n = 22). Concentration of glucose, protein, cholesterol (CHOL), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triacylglycerol (TAG) in the samples was determined., Results: Glucose concentration in serum was higher than in cysts and follicles (p < 0.01) and glucose concentration in cysts was higher than in follicles (p < 0.01). Differences were also observed between the concentration of glucose in serum of cysts-bearing and non-cysts-bearing sows (p < 0.01). Protein concentration in cysts and follicles was lower than in serum (p < 0.01). Concentration of cholesterol in the serum of cysts-bearing sows and non-cysts-bearing sows was higher than the one in cysts and follicles (p < 0.01). Cholesterol concentration in the serum of cysts-bearing sows was higher than the one in non-cysts-bearing sows (p < 0.01). Concentration of HDL in serum of both cysts-bearing and non-cysts-bearing sows was also higher than the one in cysts and follicles (p < 0.01). Cysts-bearing sows had a higher concentration of HDL in the serum than non-cysts-bearing sows. Differences were also observed between the concentration of HDL in cysts and the one in follicles (p < 0.05). LDL was determined not to be present in either cysts or pre-ovulatory follicles. TAG concentration in the serum of cysts-bearing sows was higher than the one in the serum of non-cysts-bearing sows (p < 0.05). Differences were also detected between the TAG concentrations in cysts and in follicles (p < 0.01)., Conclusion: The differences in the biochemical composition of the fluid in follicular cysts and pre-ovulatory follicles point to the variable intensification of the course of metabolic processes in pathological and physiological ovarian structures.

Objective: p53 gene mutations are frequently identified in ovarian cancer tissue. The aim of this study was to investigate whether wild type or mutated genomic DNA can be identified in ovarian cystic fluid specimens., Study Design: Forty-eight Japanese patients with cystic ovarian tumors (30 benign cysts, 8 borderline malignant tumors, and 10 cancers) were investigated. Cystic fluid and tumor tissue were obtained during surgery. After DNA extraction from the cystic fluid, polymerase chain reaction (PCR) and sequence analysis for exons 4-9 of the p53 gene was performed. In two cases of mucinous cystic tumor of borderline malignancy and endometrioid adenocarcinoma, the p53 gene sequences were determined. Immunohistochemical staining for abnormal p53 gene product was also performed., Results: DNA was successfully extracted from all cystic fluid specimens. Furthermore, exons 4-9 of the p53 gene could be identified by electrophoresis from all samples. In a mucinous cystic tumor of borderline malignancy, one point mutation was identified at codon 223 in exon 6 (CCT → CTT) of the p53 gene. Aberrant p53 gene product was also observed in the tumor cells by immunohistochemical staining. Moreover, in another case of endometrial adenocarcinoma, a point mutation at codon 245 in exon 7 (GGC → AGC) was detected by the direct sequencing of the amplified Exon. Notably, the mutation was not present in the peripheral blood (PB) sample and tissue specimens from the patient., Conclusion: In cystic ovarian tumors, cystic fluid may provide informative material for molecular studies since it reflects the p53 status of tumor tissue in the cyst wall. This system might help to identify ovarian malignancy without resection of the tumor tissues., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

SELDI-TOF MS analysis of cyst fluids identified 95 peaks that discriminate malignant, borderline, and benign ovarian tumors. Three prominent peaks, which correspond to calgranulin A (m/z 10847) and two isoforms of calgranulin B (m/z 12717 and 13294), have higher concentrations in borderline and malignant cyst fluids. Together, calgranulin A and B distinguish borderline and malignant tumors from benign tumors with 28.6% and 63.6% sensitivity for early stage disease, respectively, at 95% specificity and with 74.8% accuracy. Ovarian cyst fluids are useful for discovering discriminatory biomarkers, such as calgranulin, which may have utility for detecting, diagnosing, and biochemically classifying ovarian tumors.

Objective: To determine whether the oncofetal protein IMP3 is detectable in endometriomas with or without histological atypia and whether IMP3 staining can be used as a triage tool to identify foci of atypical endometriosis in doubtful cases., Design: Retrospective study., Setting: Academic department and referral center for endometriosis., Patient(s): A consecutive series of 516 women who underwent excision of 874 endometriomas., Intervention(s): Histological review by three expert pathologists and immunohistochemical staining for IMP3., Main Outcome Measure(s): Test performance of IMP3 immunohistochemistry versus first-round histology., Result(s): The prevalence of atypical endometriosis was 1.7% (95% confidence interval [CI], 0.9%-3.3%) based on the number of women and 1.0% (95% CI, 0.5%-1.9%) based on the number of cysts. Three cases of atypical endometriosis were identified at first-round histological examination. Immunohistochemistry detected seven of the eight cases diagnosed as preneoplastic atypia at second-round histology and one case diagnosed as reactive atypia at second-round histology. The sensitivity of first-round histology was 33.3%, compared with 88.9% of IMP3 immunohistochemistry., Conclusion(s): Immunohistochemical staining for IMP3 expression is a simple, inexpensive, and sensitive test that can be used in routine clinical practice as a triage tool to discriminate between cytological/structural atypia and confounding benign conditions., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The aim of the study was to examine the concentrations of the soluble receptors and their ligands of CD30/CD30L and CD40/CD40L systems in the serum of women with ovarian tumor and in the ovarian cyst fluid of women with Cystadenoma serosum. The study included 120 women with ovarian tumors. As a control, sera were obtained from 60 healthy female volunteers. Concentrations of the sCD30, sCD30L, sCD40 and sCD40L in the serum and the ovarian cyst fluid were measured by ELISA enzyme-linked immunosorbent assay. Concentrations of both sCD30 and sCD30L in serum of women with ovarian tumors were significantly higher than in control (p < 0.0001). The highest serum receptor and its ligand levels were observed in women with ovarian cancer (p < 0.0001). Moreover, results showed significantly increased levels of sCD40 and sCD40L serum in women with ovarian tumors, as compared to the control group (p < 0.0001). The highest concentration of sCD40 in the serum of women with ovarian cancer and sCD40L in serum of women with Teratoma maturum (p < 0.0001) were observed. Impaired apoptosis among women with ovarian tumors is associated with the impairments of soluble CD30/CD30L and CD40/CD40L systems. Measurement of studied parameter concentrations in serum of women with ovarian tumors has been suggested to be a potential tool in monitoring of inflammatory. Evaluation of sCD30, sCD30L and sCD40 might be an early diagnostic marker in patients with the ovarian cancer. Concentrations of the studied parameters in the ovarian cyst fluid higher than the serum values suggest local suppression of the immune response. However, the final evaluation of the importance of measurement of serum levels of them requires further investigation., (Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Ovarian tumor composed only of Brenner tumor and struma ovarii is very rare; only 6 cases have been reported in the English literature, to the best of the author's knowledge. A 66-year-old woman underwent right oophorectomy because of torsion of right ovarian cyst. Macroscopically, the ovarian cyst was hemorrhagic and red. Cystic content was hemorrhagic fluid. Microscopically, the cyst walls were composed only of Brenner tumor (50% in area) and struma ovarii (50% in area). Hemorrhage and ischemic changes were seen. Other elements were not recognized. No malignant transformation was noted. These two elements were separately present, and no mergers between them were recognized. Immunohistochemically, the Brenner tumor element was positive for cytokeratins (AE1/3 and CAM5.2) and Ki67 (labeling=3%), but negative for thyroglobulin, TTF-1, p53, CA125, and vimentin. The struma ovarii element was positive for cytokeratins (AE1/3 and CAM5.2), thyroglobulin, TTF-1 and Ki67 (labeling=5%), but negative for p53, CA125 and vimentin. The findings suggests that there were cases of ovarian cyst composed only of Brenner tumor and struma ovarii, that such a case may be monodermal mature cystic teratoma or the Brenner tumor element was derived from surface epithelium in the preexisting struma ovarii, and that such a tumor manifest as cystic torsion.

The aim of this study was to evaluate the relationship between ovarian cysts and concentrations of ovarian steroid hormones: 17beta-estradiol (E(2)), progesterone (P(4)), testosterone (T), and androstendione (A(4)) both in blood plasma and in cysts and morphological state of the ovarian cortex in sows. Females were divided into three groups: PCO (sows with polycystical ovaries), OO (sows with oligocystic ovaries) and control (sows without ovarian cysts). The ovaries for evaluations were collected after slaughtering of 18 multiparous sows. Between the PCO and OO animals, statistically significant differences in numbers of the follicular cysts (FC) (8.6 vs. 1.5), follicular theca-lutein cysts (FTLC) (8.0 vs. 2.0), follicular lutein cysts (FLC) (4.5 vs. 2.0) and corpus luteum cysts (CLC) (1.7 vs. 0.4) (P< or =0.01) were noted. In the PCO sows the most common kinds of cysts were FC and FTLC (8.6 and 8.0) whilst in OO sows the cysts occurred on their ovaries on a similar level (FC - 1.6, FTLC - 2.0, FLC - 2.0). Existence of more than 10 ovarian cysts in the sows significantly decreases the frequency of physiological ovarian follicles (primary, growing and maturing) and significantly increases the pathological process of atresia on all stages of ovarian follicles development (P< or =0.01). The study did not reveal any effect of growing or decreasing number of ovarian cyst on concentrations of E(2) and P(4) in blood plasma of sows. Polycystical ovaries significantly decreased concentrations of A(4) but increased the concentration of T in blood plasma (P< or =0.01). The general presence of ovarian cysts considerably positively correlated with concentrations of E(2), T and A(4) from cysts' fluid, of all kinds of ovarian cysts and atresia of primary follicles (a correlation coefficient r from 0.72 up to 0.97, P< or =0.05). The phenomenon of ovarian cysts significantly negatively correlated with all generations of ovarian follicles (P< or =0.05)., (2010 Elsevier B.V. All rights reserved.)

Background: A major step in cancer formation involves the degradation of the extracellular matrix, mediated by multiple degradative actions of (lysosomal) proteases. Extracellular release of lysosomal proteases (cathepsins) and their inhibitors has been associated with the development and progression of several types of cancer. We investigated whether cathepsins in ovarian cyst fluid (oCF) were associated with disease outcome in patients with epithelial ovarian cancer (EOC)., Materials and Methods: The levels of cathepsin B (CatB), H (CatH), L (CatL) and X (CatX) and their most abundant extracellular inhibitor cystatin C (CysC) were determined in oCF of 50 EOC patients by quantitative ELISAs. The cathepsin levels and ratios between cathepsins and CysC were related to clinicopathological parameters (Mann-Whitney U and Kruskal-Wallis tests) and survival (Cox Regression analysis)., Results: Median (25th-75th percentile) levels of cathepsin B, H, L, X and CysC in oCF were 97 (42-203), 18 (12-32), 61 (37-108), 20 (13-47) and 657 (501-805) ng mL(-1) respectively. Ratio of CysC/CatB was significantly lower for patients with metastatic compared with localised EOC (P = 0.025). Ratios of CysC/CatH and CysC/CatX differed significantly between histological subtypes (P = 0.012 and P = 0.035 respectively) and were significantly higher for high-grade tumours compared with low-grade tumours (P = 0.031 and P = 0.039 respectively). Neither cathepsins nor their ratios were significant predictors of survival for EOC patients., Conclusions: Ratios between CysC and cathepsins in oCF differed significantly between important clinicopathological subgroups. We believe that a complex cascade of proteolytic events, in which cathepsins play different roles, might be responsible for progression and metastasis in EOC.

Background: In humans, N-acetyl L-aspartate (NAA) has not been detected in other tissues than the brain. The physiological function of NAA is yet undefined. Recently, it has been suggested that NAA may function as a molecular water pump, responsible for the removal of large amounts of water from the human brain. Ovarian tumors typically present as large cystic masses with considerable fluid accumulation., Methodology and Principal Findings: Using Gas Chromatography-Mass Spectrometry, we demonstrated that NAA was present in a high micromolar concentration in oCF of epithelial ovarian tumors (EOTs) of serous histology, sometimes in the same range as found in the extracellular space of the human brain. In contrast, oCF of EOTs with a mucinous, endometrioid and clear cell histological subtype contained a low micromolar concentration of NAA. Serous EOTs have a cellular differentiation pattern which resembles the lining of the fallopian tube and differs from the other histological subtypes. The NAA concentration in two samples of fluid accumulation in the fallopian tube (hydrosalpinx) was in the same ranges as NAA found in oCF of serous EOTs. The NAA concentration in oCF of patients with serous EOTs was mostly 10 to 50 fold higher than their normal serum NAA concentration, whereas in patients with other EOT subtypes, serum and cyst fluid NAA concentration was comparable., Conclusions and Significance: The high concentration of NAA in cyst fluid of serous EOTs and low serum concentrations of NAA in these patients, suggest a local production of NAA in serous EOTs. Our findings provide the first identification of NAA concentrations high enough to suggest local production outside the human brain. Our findings contribute to the ongoing research understanding the physiological function of NAA in the human body.

Most ovarian tumors contain ovarian cyst fluid (oCF) which can be easily obtained during surgery. This is the first study that explored if CA 125 in oCF could be of prognostic value for patients with epithelial ovarian cancer (EOC). Of 54 patients with primary EOC, oCF and preoperative serum were collected and clinicopathological data were retrospectively obtained. CA 125 was measured with the commercially available CA 125 assay. CA 125 in oCF (n=54, median: 55,500 U/ml, range: 590-10,200,000 U/ml) was always higher than in the corresponding serum (n=51, median: 179 U/ml, range: 13-11,000 U/ml) (p<0.001) and values were moderately correlated (R=0.337, p=0.016). CA 125 in oCF was associated with histology (p<0.001) and tumor grade (p=0.038). High levels of oCF CA 125 (>median) were significantly associated with a poor disease-free survival (DFS) (log-rank p=0.002 and p=0.005 univariate Cox-regression). Other factors associated with a poor DFS in univariate analysis were advanced FIGO stage, suboptimal debulking (both p<0.001), high tumor grade (p=0.025), serous histology (p=0.003) and high serum (>media) CA 125 (p=0.009). In multivariate analysis, only FIGO stage was of independent predictive value. These findings indicate that, although high levels of oCF CA 125 were significantly associated with a poor survival of EOC patients, CA 125 in oCF was not of independent predictive value and might therefore not be useful as a prognostic biomarker for EOC.

High activity of ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine synthesis, is typically present in rapidly proliferating normal and malignant cells. The mitotically inactive steroidogenic cells in rodent testis and ovaries, however, also display high ODC activity. The activity of ODC in these cells responds to luteinizing hormone, and inhibition of ODC reduces the production of steroid hormones. Polyamines and ODC also control proliferation of germ cells and spermiogenesis. The activity of ODC, especially in proliferating cells, is regulated by antizyme inhibitor (AZIN). This protein displaces ODC from a complex with its inhibitor, antizyme. We have previously identified and cloned a second AZIN, i.e. antizyme inhibitor 2 (AZIN2), which has the highest levels of expression in brain and in testis. In the present study, we have used immunohistochemistry and in situ hybridization to localize the expression of AZIN2 in human gonads. We found a robust expression of AZIN2 in steroidogenic cells: testicular Leydig cells and Leydig cell tumors, in ovarian luteinized cells lining corpus luteum cysts, and in hilus cells. The results suggest that AZIN2 is not primarily involved in regulating the proliferation of the germinal epithelium, indicating a different role for AZIN1 and AZIN2 in the regulation of ODC. The localization of AZIN2 implies possible involvement in the gonadal synthesis and/or release of steroid hormones.

An unassigned and prominent resonance in the region from delta 2.0-2.1 ppm has frequently been found in the in vivo MR spectra of cancer patients. We demonstrated the presence of this resonance with in vivo MRS in the cyst fluid of a patient with an ovarian tumor. (1)H-NMRS on the aspirated cyst fluid of this patient confirmed the observation. A complex of resonances was observed between 2.0 and 2.1 ppm. It was also present in 11 additional ovarian cyst fluid samples randomly chosen from our biobank. The resonance complex was significantly more prominent in samples from mucinous tumors than in samples from other histological subtypes. A macromolecule (>10 kDa) was found responsible for this complex of resonances. A correlation spectroscopy (COSY) experiment revealed cross peaks of two different types of bound sialic acid suggesting that N-glycans from glycoproteins and/or glycolipids cause this resonance complex. In the literature, plasma alpha-1 acid glycoprotein (AGP), known for its high content of N-linked glycans, has been suggested to contribute to the delta 2.0-2.1 spectral region. The AGP cyst fluid concentration did not correlate significantly with the peak height of the delta 2.0-2.1 resonance complex in our study. AGP may be partly responsible for the resonance complex but other N-acetylated glycoproteins and/or glycolipids also contribute. After deproteinization of the cyst fluid, N-acetyl-L-aspartic acid (NAA) was found to contribute significantly to the signal in this spectral region in three of the 12 samples. GC-MS independently confirmed the presence of NAA in high concentration in the three samples, which all derived from benign serous tumors. We conclude that both NAA and N-acetyl groups from glycoproteins and/or glycolipids may contribute to the delta 2.0-2.1 ppm resonance complex in ovarian cyst fluid. This spectral region seems to contain resonances from biomarkers that provide relevant clinical information on the type of ovarian tumor.

The purpose of this study was to estimate the expression and relative amounts of estrogen (ER) and progesterone receptors (PR) and their isoforms as well as heat shock protein 70 (HSP70) in ovaries of rats with induced cystic ovarian disease (COD). Primary, secondary, tertiary, atretic and cystic follicles were evaluated by immunohistochemistry and total ovarian proteins were analyzed by Western blot. In the granulosa layer, growing and cystic follicles in the treated group have a higher expression of ERalpha than growing follicles of control individuals. In the theca interna layer, tertiary follicles presented a significantly higher expression of ERalpha in the treated group. An increase in total ERalpha protein was detected in the treated group. Granulosa cells of all growing, atretic and cystic follicles show a lower expression of ERbeta in animals with COD, and the total protein expression of ERbeta was lower in this group. The expression of PR was lower in the granulosa cell layer of tertiary and cystic follicles in treated animals, and theca interna layer had less intense immunostaining in this group. Although there were no differences in the expression of PR-B by Western blotting, the expression of PR-A was higher and the expression of PR-C was smaller in the treated group. An intense HSP70 immunostaining was observed in the cells of cystic follicles. By Western blotting, higher protein expression of HSP70 was detected in the ovarian samples of the control group than those of the treated ones. Ovaries of animals with COD exhibited an altered steroid receptor expression and subtype balance as compared with control animals, and an increase in HSP70 immunoexpression.

Detoxification enzymes, especially glutathione S-transferase P1-1 (GSTP1-1), have been implicated in resistance to platinum-based chemotherapy. We studied GSTP1-1 levels in ovarian cyst fluid (oCF), obtained during surgery before chemotherapy, of patients with epithelial ovarian cancer and clinical outcomes were correlated. GSTP1-1 was determined by ELISA in oCF of 56 patients with epithelial ovarian cancer and 109 noncancer controls (21 borderline and 88 benign ovarian tumors). Differences in median GSTP1-1 between clinicopathologic subgroups were studied using Mann-Whitney U and Kruskal Wallis tests. Differences in disease-free (DFS) and overall survival (OS) between groups were analyzed by applying Kaplan-Meyer estimates and log-rank tests. Univariate and multivariate analysis were done using Cox proportional hazard model. Significantly higher levels of GSTP1-1 were found in the oCF of malignant (median, 383; range, 10-32,695 ng/mL) compared with benign (median, 20; range, 0-1,128 ng/mL) ovarian tumors (P < 0.01). Significantly higher GSTP1-1 levels were found in patients with advanced International Federation of Gynaecologists and Obstetricians stage (P = 0.01), high-grade tumors (P = 0.44), and/or high levels of preoperative CA 125 (P = 0.01). Of patients who received chemotherapy (stage, >or=Ic; n = 30), high GSTP1-1 levels were significantly associated with a poor DFS and OS (log-rank P = 0.047 and P = 0.033, respectively). International Federation of Gynaecologists and Obstetricians stage was the only independent predictor for DFS. GSTP1-1 was the only independent predictor for OS.

Although the individual human blood group A and B determinants are well defined, their co-expression pattern on a particular glycan carrier in individuals of blood group AB status has not been delineated. To address this issue, complex O-glycans were isolated from two distinct sources of human ovarian cyst glycoproteins (HOC 89 and Cyst 19) and profiled by advanced MS analyses, in conjunction with defining their binding characteristics against a panel of lectins and monoclonal antibodies. The major O-glycans of HOC 89 were found to correspond to sialyl Tn, mono- and di-sialyl T structures, whereas those of Cyst 19 were apparently more heterogeneous and extended to larger sizes. A minimal structure that carries both A and B determinants on the same molecule was identified, in which the A epitope is attached directly to the core GalNAc, whereas the B epitope is preferentially located on the six arms of a core 2 structure. Both arms can be further extended with internal fucosylation that appears to be restricted to those non-sialylated chains already carrying the terminal ABH determinants, thus giving rise to rather prominent A/B-Le(b/y) glycotopes on larger O-glycans.

Objective: To investigate the common characteristics of a rare entity of ovarian cystic teratoma with intracystic floating balls in conjunction with a case., Design: Case report., Setting: University hospital., Patient(s): A 41-year-old woman with abdominal discomfort and a 2-year obscure history of an ovarian cyst., Intervention(s): Right salpingo-oopherectomy by laparotomy., Main Outcome Measure(s): Ultrasonography and magnetic resonance imaging (MRI)., Result(s): Ultrasonographic examination revealed a cystic mass (>10 cm) with a unique appearance of multiple floating balls on the lower right quadrant of the abdomen. The MRI showed the same balls with a slightly high fat content. Histopathological diagnosis was mature cystic teratoma and the balls were mostly made of keratin., Conclusion(s): The appearance of intracystic floating balls is rarely seen but is pathognomonic for mature cystic teratoma. When this typical appearance is found on ultrasonography the value of other diagnostic tests, such as tumor markers, serological tests for echinococcosis, computerized tomography (CT), and MRI, can be considered as limited.

The aims of this study were to determine the concentrations of the progesterone, oestradiol-17-beta, vitamin A, C and beta-carotene in plasma and cyst fluid and to relate these values with cystic diameter and membrane thickness of Holstein cattle with ovarian luteal cyst. 1650 Holstein cows were examined for the presence of the ovarian cyst and luteal and follicular cystic ovaries were obtained following slaughtering in personal slaughterhouse in Konya-Turkey. 15 Luteal and 15 follicular cystic ovaries were distinguished by rectal palpation and by post mortem ultrasonographic examination. Plasma and cyst fluid, hormone and vitamin analyses were carried out by EIA method and spectrophotometric measurement respectively. Although there was no relationship between beta-carotene and vitamin A in plasma and cyst fluid of both cyst type and hormone concentrations, the vitamin C concentration of cyst fluid was found significantly higher in luteal cyst than in follicular cyst. Moreover, there is a positive correlation among values of the vitamin C concentrations of cyst fluid and cystic membrane thickness, plasma and the cyst fluid progesterone concentrations, but there is a negative correlation among the vitamin C concentrations of cystic fluid and oestradiol 17beta levels of plasma and cyst fluid. In conclusion, vitamin C concentration of cyst fluid supported ultrasonographic and endocrinologic findings. Also, it can be postulated that vitamin C is probably effective on progesterone synthesis in the luteal tissue of cyst.

Purpose: Endometriotic cysts are known to transform into ovarian cancers, such as clear cell and endometrioid carcinomas. We hypothesized that an iron-rich environment produced by the repetition of hemorrhage in the endometriotic cysts during the reproductive period may play a crucial role in carcinogenesis in the cysts through the iron-induced persistent oxidative stress., Experimental Design: Contents of human ovarian cysts, including 21 endometriotic cysts, 4 clear cell carcinomas, and 11 nonendometriotic cysts, were analyzed for the concentrations of free "catalytic" iron, lactose dehydrogenase, potential antioxidant, lipid peroxide, and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Iron deposition and 8-OHdG levels were also analyzed histologically. Reactive oxygen species and the mutagenicity of the contents in endometriotic cyst were determined in vitro., Results: The concentration of free iron in endometriotic cysts (100.9 mmol/L) was significantly higher than that in nonendometriotic cysts (0.075 mmol/L; P < 0.01). The average concentrations of lactose dehydrogenase, potential antioxidant, lipid peroxide, and 8-OHdG were also significantly higher in endometriotic cysts (P < 0.01). There was a correlation between the concentration of free iron and that of 8-OHdG (P < 0.01). Histologically, we could observe iron deposits more abundantly in endometriotic cysts than in nonendometriotic cysts (P < 0.01). The level of 8-OHdG in carcinoma associated with endometriosis was higher than that of carcinoma without endometriosis (P < 0.05). In vitro analyses showed that the contents of endometriotic cyst could produce more reactive oxygen species and could induce gene mutations more frequently than the contents in the other cysts., Conclusions: Abundant free iron in the contents of endometriotic cysts was strongly associated with greater oxidative stress and frequent DNA mutations. A long-standing history of the RBCs accumulated in the ovarian endometriotic cysts during the reproductive period produces oxidative stress that is a possible cause for the malignant change of the endometriotic cyst.

Objectives: Unfavourable prognosis of ovarian cancer is due to prompt progression, advanced stage at time of diagnosis and chemoresistance. No protein tissue prognosticators of ovarian cancer are in clinical use yet. YB-1 belongs to a family of "cold shock proteins" and participates at gene expression control at several levels. High expression of YB-1 in tumour tissue correlates with unfavourable prognosis and chemoresistance in some malignant neoplasms., The Aim: of this study was to determine the expression of YB-1 in benign and malignant ovarian neoplasms and to correlate the expression of YB-1 with clinical indicators of cancer progression., Methods: Specimens of 11 benign ovarian cysts and 14 cystadenocarcinomas of the ovary were obtained.YB-1 expression was determined by immunohistochemistry. Staging of ovarian cancer was performed according to FIGO., Results: Mean YB-1 expression levels in benign and malignant tumours were 5.36 +/- 4.1 and 2.86 +/- 4.18 points respectively and were not significantly different (p=0.18). No correlation between FIGO stage and expression of YB-1 was found in the group of ovarian cancers, either (p=0.32)., Conclusions: This study demonstrates that YB-1 is expressed both in benign and malignant ovarian tumors. Although there we didn't found any correlation between YB-1 expression and FIGO stage, YB-1 could be useful in the prognosis recurrence after chemotherapy.

Aims and Background: Cells and soluble mediators obtained from tumor effusions are useful in evaluating the tumor microenvironment. Our aim was to examine cytologically and to quantify the leukocyte infiltrate, nitric oxide, cytokines and tumor markers in the intracystic fluid from patients with a cystic adnexal mass, for a possible differentiation between benign and malignant findings., Methods and Study Design: Sixty-six women who had their cystic fluids collected were prospectively divided into benign tumor (22, 33.3%), malignant tumor (10, 15.2%) or other gynecological alterations (34, 51.5%). Cytology, total and differential leukocyte counts were determined by light microscopy. Tumor markers, cytokines and nitric oxide were assayed in the supernatants using the Immulite system, ELISA and Griess reaction, respectively., Results: The sensitivity and specificity of the cytological analysis was 66.7% and 97.7%, respectively. The levels of CA 19.9, CA 15.3, alpha-fetoprotein, carcinoembryonic antigen, progesterone and beta-HCG were significantly higher in the benign and/or malignant group than in the other gynecological alterations. Also, the local concentrations of CA 15.3 and beta-HCG were significantly higher in malignant than in benign tumors. In malignant tumors, increased leukocyte counts and higher concentrations of IL-6, IL-10 and nitric oxide were detected than in benign tumors or other gynecological alterations., Conclusions: In malignant tumors, the microenvironment could be differentiated from benign tumors or other gynecological alterations by cystic fluid analysis.

Objective: To investigate the expression of adrenomedullin (AM) in benign and malignant ovarian tissues and its correlation with estrogen receptors (ERs) mRNA status., Study Design: Ovarian carcinoma cell lines, normal ovaries, serous cysts and cancers were analyzed using real-time polymerase chain reaction (PCR) in order to quantify adrenomedullin and ERs mRNAs expression. Some ovarian samples were submitted to laser-capture microdissection to determine the differential expression of target genes in epithelium and stroma., Results: Ovarian cancer cells express adrenomedullin mRNA for both the ligand and receptor and produce the peptide. In tumors, the ER alpha/beta ratio was higher than in other tissues. Correlations were found between ER alpha and ER beta mRNA and adrenomedullin mRNA expression in tumors., Conclusion: Adrenomedullin may be involved in both normal and malignant tissue growth through both vascular and growth factor effects. Because of the correlations with ERs status, there is emerging evidence that ovarian cancer is endocrine-related.

Objectives: The epithelial ovarian tumors arise from the single layer of epithelial cells that line the ovarian surface or from underlying inclusion cysts. One from many theories of oncogenesis has been proposed that benign, borderline and invasive tumors represent sequential stages in the growth of an ovarian cancer, and p53 tumor suppressor gene mutation is the most common molecular genetic alteration. Because locus of p53 gene is located on 17 chromosome we performed the cytogenic analysis of tumor tissues., Design: Analysis of mutated p53 protein expression and chromosomal aberrations in tissues of benign tumors and epithelial ovarian carcinomas., Material and Methods: Tissue samples from 19 women with benign and 17 women with invasive epithelial ovarian cancers were obtained for the study at the time of surgical procedures. From among benign tumors 12 were serous cystadenomas, 5 were endometrial cysts and 2 adult teratomas. All cases of invasive epithelial ovarian carcinomas were histologically recognized as serous adenocarcinomas, and were staged on I (9 cases), II (5 cases) and III (3 cases), according to the FIGO guidelines for ovarian cancers. Frozen tissue samples were stained immunohistochemically for mutated p53 protein using commercial monoclonal antibodies and standard detecting system. The fresh tumor samples were prepared for cytogenic analysis according to standard protocol., Results: Among the all benign ovarian tumors overexpression of mutated form of p53 protein was not seen in any cases, but was noted in 6 cases in I stage and in all cases in II and III stages of advanced ovarian cancers. In 1 case of benign ovarian tumor deletion of X chromosome was observed. Most common numerical changes were observed in ovarian carcinomas e.g. loss of 8, 13, 17, and 22 chromosomes. Other chromosomes were involved at least once in structural rearrangements and several breakpoint cluster regions were identified: 19p13, 11p13-15, 1q21-23, 1p36, 19q13, and 6q21-23., Conclusions: The mutated form of p53 protein is often expressed in ovarian epithelial carcinoma tissues. This protein are unable to function effectively to inhibit proliferation and accumulate in the cells because is resistant to degradation. In tissues of ovarian carcinomas many chromosomal nondisjunctions (monosomics) and multiple structural rearrangements were observed, what means of genetically nonstable cell lines of neoplasms and probably it heterogenous origin.

Proteolytic enzymes, such as matrix metalloproteinases (MMPs) and tumor-associated trypsinogens (TAT), play a pivotal role in tumor invasion and metastasis. Among MMPs, the interstitial collagenases (MMP-1, -8 and -13) can initiate collagenolysis. In this study, we have studied the levels of MMP-1, -8 and -13 in relation to the level of trypsinogen-2 in fluid from benign and malignant ovarian cysts. Elevated MMP-8 levels occur in many ovarian cyst fluids, and high MMP-8 levels are associated with malignancy. The concentrations of trypsinogen-2 correlate with those of MMP-8, but it remains to be shown whether trypsin-2 plays a role as its activator in vivo. The strong expression of MMP-8 over MMP-1 and MMP-13 in malignant ovarian tumors may indicate that MMP-8 participates in the protease cascades associated with the invasiveness of ovarian tumors., (Copyright 2003 S. Karger AG, Basel)

Objective: To investigate the clinical value of the serum CA19-9 level in comparison with the serum CA125 level for diagnosing and determining the severity of endometriosis., Design: Retrospective study., Setting: Department of Comprehensive Reproductive Medicine in a university hospital., Patient(s): One hundred one women with endometriosis and 22 without endometriosis participated in this study., Intervention(s): Blood samples were collected before the operation (laparoscopy, oophrectomy, cystectomy, and/or hysterectomy), and tissue samples of ovarian chocolate cysts were collected during the operation., Main Outcome Measure(s): The serum CA19-9 and CA125 levels and the localization of these antigens in ovarian chocolate cysts., Result(s): The mean serum CA19-9 levels in patients at all stages of endometriosis were significantly higher than those in patients without endometriosis, and serum CA19-9 levels significantly correlated with the Revised American Fertility Society classification scores. Intense staining of CA19-9 was observed in 15 of the 20 samples of ovarian chocolate cysts., Conclusion(s): CA19-9 is a useful marker for determining the severity of endometriosis.

To determine whether Brenner tumors and transitional cell carcinomas (TCCs) of the ovary are urothelial in type, the immunoprofiles of 14 Brenner tumors, including three malignant examples, and eight ovarian TCCs were compared with those of Walthard nests, urothelium, 12 urinary bladder TCCs and 17 ovarian adenocarcinomas (serous, endometrioid, mucinous, and undifferentiated type). The immunohistochemical stains used included those for cytokeratins CKs 5/6, CK7, CK8, CK13, and CK20, vimentin, CA125, and the specific urothelial differentiation marker uroplakin III. CK7 and CK8 were broadly expressed in most tumors of ovary and bladder examined, while vimentin was focally present in some ovarian TCCs and adenocarcinomas. As in normal and neoplastic bladder urothelium, urothelial markers, including uroplakin III, CK13, and CK20, were detected in the epithelial nests of Brenner tumors. Brenner tumor cells also expressed uroplakins Ia and II. CA125 was observed focally in some Brenner tumors. In contrast, TCCs of the ovary and Walthard nests lacked uroplakins and were essentially negative for CK20 and CK13 but quite strongly expressed CA125. This immunophenotype closely resembled that found in ovarian adenocarcinomas. Thus, it appears that the only true urothelial-type ovarian neoplasm is the Brenner tumor, whereas ovarian TCC most likely represents a poorly differentiated adenocarcinoma with a morphologic transitional cell pattern. These results may explain the controversies as expressed in the recent literature concerning TCC of the ovary and establish its place among the ovarian adenocarcinomas of müllerian type.

Background: The purpose of the current study was to determine vascular endothelial growth factor (VEGF) concentrations in cyst fluid from malignant, borderline, and benign ovarian tumors, and to correlate these data with preoperative serum VEGF concentrations and clinicopathologic characteristics., Methods: One hundred seven ovarian cysts were removed and punctured for cyst fluid collection. Histologic diagnosis revealed 25 malignant, 12 borderline, and 70 benign ovarian tumors. The VEGF concentrations of all the cyst fluid specimens as well as in 37 preoperatively collected serum samples were determined by making use of a sandwich type double determinant enzyme linked immunoadsorbent assay based on a combination of 4 polyclonal antibodies., Results: Statistically significantly higher VEGF concentrations were found in cyst fluid from malignant (median, 21.5 microg/L) compared with borderline (median, 3.2 microg/L; P = 0.01) or benign tumors (median, 1.3 microg/L; P < 0.0001). Preoperative serum VEGF concentrations were significantly higher in patients with malignant (median, 0.63 microg/L; range, 0.016-17.7 microg/L) compared with nonmalignant tumors (median, 0.28 microg/L; range, 0.016-0.89 microg/L; P = 0.008). A significant correlation of preoperative serum VEGF was found with VEGF cyst fluid concentrations (r = 0.38; P = 0.02). Significantly higher VEGF cyst fluid concentrations were found in serous malignant (median, 31.9 microg/L) compared with mucinous malignant tumors (median, 4.7 microg/L; P = 0.004). Not significant, though higher median VEGF cyst fluid concentrations were found in advanced International Federation of Gynecology and Obstetrics (FIGO) Stage II, III, and IV, histologic Grade 2 and 3, patients with residual tumor greater than 2 cm, with malignant cells in ascites or peritoneal washings, or with recurrent disease, as compared with FIGO Stage I, histologic grade 1, patients with less than or equal to 2-cm residual tumor, without malignant cells in ascites/peritoneal washings, or without recurrent disease, respectively., Conclusions: It has become clear from the increased study sample that ovarian tumors of different histologic etiology vary in VEGF cyst fluid concentrations, with the highest VEGF cyst fluid concentrations in malignant tumors. The prognostic significance of VEGF cyst fluid concentrations in advanced FIGO stage seems to be of limited value but may be important in the selection of high risk FIGO Stage I and borderline types. Data from this study indicate a possible role for VEGF as a serum tumor marker.

Objective: Methotrexate has been documented to accumulate in pleural effusions and ascitic fluid, resulting in severe local and systemic toxicity. In the following case report, we publish results of intraoperative measurements of methotrexate levels in serum and an ovarian cyst and attempt to determine if ovarian cysts similarly act as a depot for methotrexate., Methods: After determining intraoperative measurements of serum and ovarian cystic levels of methotrexate, we compared demonstrated pharmacokinetics to those expected by using pharmacokinetic systems analysis software., Results: Intraoperative measurement of methotrexate levels on day 3 of a 5-day methotrexate regimen revealed a serum methotrexate concentration of 1.6 x 10(-7) M and a concentration of 3.1 x 10(-7) M within the 166.4 ml ovarian cyst., Conclusions: The measured levels demonstrate that methotrexate is sequestered within an ovarian cyst resulting in higher local drug levels. Our pharmacokinetic analysis suggests that methotrexate doses less than 100 mg/m2 can be safely administered to patients with small ovarian cysts. However, computed simulations support the possibility of local and systemic toxicity arising from large ovarian cysts when using high doses of methotrexate., (Copyright 1999 Academic Press.)

Due to the difficulties in separating malignant and benign ovarian cysts by transvaginal ultrasound and other techniques, there is a need for biochemical markers in serum or cyst fluids. In the present study we have evaluated the levels of the chemokine interleukin-8 (IL-8) in ovarian cysts. IL-8 is known to be expressed in the normal ovary and to influence proliferation and angiogenesis of several nonovarian types of tumors. Cyst fluids from benign (n = 15) and malignant (n = 13) ovarian tumors were analyzed. The levels of IL-8 were found to be significantly (13-fold) higher in cyst fluids from malignant tumors (18.1 +/- 7.5 ng/ml; mean +/- SE) compared to benign cysts (1.3 +/- 0.7 ng/ml). The plasma levels of IL-8 were considerably lower (2.9 and 0.3% of levels in benign and malignant cyst fluids, respectively) than in cyst fluids. No difference in the plasma levels of patients with benign or malignant tumor could be detected. In contrast, the levels of CA 125 were significantly higher in plasma of patients with malignant disease with the inverse relation in cyst fluids. In conclusion, the levels of IL-8 are markedly elevated in cyst fluid from malignant tumors compared to benign. This specific increase indicates a role for this cytokine in ovarian tumor biology., (Copyright 1998 Academic Press.)

Gonadotropins can stimulate ovarian cancer growth in cell cultures. Corresponding LH/hCG receptors have been demonstrated in ovarian cancer. However, reduction of elevated serum gonadotropins by GnRH analogs in ovarian cancer patients did not lead to growth restriction, which means that serum levels of gonadotropins may not play the most important role in ovarian cancer. We therefore analyzed the LH and FSH concentrations in cyst fluids of ovarian cancer. Patients with preoperatively diagnosed cystic ovarian tumors were eligible for the study. Serum samples of the patients were obtained during surgery, while the fluids within the cysts were aspirated after surgical removal of the tumor. FSH and LH levels in serum and cyst fluids were measured using single antibody EIA (Boehringer Mannheim GmbH, Germany). Cyst fluids and sera of 108 patients were evaluated. While there were no significant differences in the FSH and LH serum concentrations, highly significant differences in the FSH and LH levels in cyst fluids were found. Only cancer cysts contained FSH and LH, while the corresponding concentrations in benign cysts were always below the measuring range of the assays. This clear division between high gonadotropin levels in cysts of serous ovarian cancer and low or absent concentrations in benign ovarian tumors further supports the hypothesis that FSH and LH may play a role in ovarian cancer; however, explanations for this surprising finding are still lacking.

Prolactin and GH have been detected within the ovary, and it has become increasingly evident that they have a role as intrafollicular regulatory factors. The aim of the present work was to gain an insight into the elements influencing intraovarian GH and PRL in bovine species and to see whether cystic degeneration was accompanied by abnormal bovine GH (bGH) and PRL (bPRL) plasma patterns. We followed the relationships between plasma and ovarian fluid bGH and bPRL concentrations over an entire year in Friesian cows whose ovaries showed distinct types of structures. To assess the presence of bGH and bPRL within ovarian cells, we assayed selected ovarian structures by immunohistochemistry. The results demonstrated that: 1) plasma and ovarian fluid hormonal concentrations were independent, and their ratio was independent of the ovarian structure classes, subclasses and period of the year; 2) in the majority of the cows the concentration of bGH in ovarian fluid was no more than 80% of the level in plasma, whereas in about half the animals bPRL concentrations were higher in the ovary than in peripheral plasma; 3) mean bPRL concentrations in ovarian fluids were significantly higher in summer than in winter; 4) immunoreactive bGH and bPRL were present within granulosa and luteal cells. Thus, it is suggested that in the cow bGH and bPRL levels in the ovary might be regulated in some way independently of the pituitary.

CA-125 is abundantly secreted from ovarian endometriotic cysts, but is not specific to endometriosis. In order to develop a new, more specific diagnostic marker for endometriosis, the iron concentrations in various ovarian cysts were assayed. The ovarian cysts were punctured and the contents aspirated laparoscopically, laparotomically, or transvaginally. The iron concentration in the ovarian cystic fluid was assayed using a spectrophotometer after protein precipitations and chromogen treatment. The iron concentrations in ovarian cysts were 69.5+/-10.4 micromol/l in serous cystadenomas, 73.5+/-29.3 in mucinous cystadenomas, 65.4+/-12.4 in dermoid cysts, and 92.5+/-18.2 micromol/l in adenocarcinomas. On the other hand, high iron concentrations were demonstrated in endometriotic cysts (1,749.6+/-41.5 micromol/l), a lutein cyst (1,393.8), hemorrhagic corpus luteum (1,957.5) and endometrioid adenocarcinomas (1,860.9+/-157.9 micromol/l). Cytological smear tests of the contents as well as histological examination allowed differential diagnosis between endometriosis and endometrioid adenocarcinoma. In conclusion, assay of the ovarian cystic iron concentration is a useful diagnostic tool for the evaluation of ovarian endometriotic cysts.

This article reports the clinicopathological and immunohistochemical findings of two cases of adenoma of the the rete ovarii (RO), one unilateral and the other bilateral, presenting with atypical histological features in the right ovary. Both tumors were incidental findings in 62- and 64-year-old patients presenting with metrorrhagia. The predominantly cystic lesions measured 2 cm and 3 cm in diameter and microscopically, they were tubulopapillary proliferations of regular columnar cells with clear cytoplasm. The stroma showed extensive differentiation of polygonal, Leydig-like cells which was associated in both cases with simple endometrial hyperplasia. In both cases rete and hilar mesonephric remnants were found in the vicinity of the lesion. The atypical lesion in one case had a complex papillary proliferation different in pattern and cellularity from a retiform Sertoli-Leydig cell tumor. It showed extensive areas of eosinophilic change, pleomorphism, and a few mitoses but did not invade the adjacent ovarian stroma. Its stroma also had steroidally active cells. The patient was alive and well after a follow-up interval of 3 years. Immunohistochemically, the lesions were diffusely positive for CAM 5.2, vimentin, epithelial membrane antigen, OC 125, OC 125, and progesterone receptors.

Background: Mucinous tumors of the ovary have been thought to originate in two ways: by müllerian-type metaplasia of surface epithelium, and as monodermal teratomas. To gain a better understanding of their pathogenesis, the authors analyzed these tumors for their expression of estrogen receptors (ER) and progesterone receptors (PR) as markers of müllerian-type differentiation and for their content of gastric-type mucin as a marker of gastric differentiation., Methods: The histochemical expression of ER, PR, and gastric-type mucin was studied in 10 specimens of the cervix with normal endocervical glands (as a representative of müllerian-derived mucin-containing cells), 3 ovary specimens with surface epithelial inclusion cysts that contained endocervical-like mucin-containing cells (representing müllerian-type metaplasia), and 47 mucinous tumors of the ovary (29 benign, 8 with low malignant potential, and 10 malignant)., Results: Normal endocervical glands expressed ER and PR and rarely expressed gastric-type mucin. Ovarian inclusion cysts showed strong expression of ER and PR in the cuboidal cells and drastically reduced expression in the endocervical-like mucin-containing cells. The cuboidal cells were negative for gastric-type mucin, but the endocervical-like mucin-containing cells expressed gastric-type mucin. Endocervical-like mucinous cells in benign and borderline mucinous tumors showed expression of PR and/or gastric-type mucin in all cases., Conclusions: The staining results for the inclusion cysts support the thesis that the endocervical-like mucinous cells encountered in the ones that express ER and PR weakly or not at all and have histochemical properties of normal gastric epithelium have their origin in metaplasia of müllerian-type epithelium. Application of the same staining methods to benign ovarian tumors and those with low malignant potential suggests strongly that similar müllerian-type metaplasia is a major pathway in their pathogenesis.

We studied the effects of different hormones on the epithelial cells of the ovaries of 11 guinea pigs. Three received testosterone, two received estrone, three megestrol, and three chorionic gonadotropin. Three control guinea pigs received sterile water. Benign epithelial cysts larger than 1.5 mm were found in six guinea pigs, three who received testosterone, one who received megestrol, and two who received chorionic gonadotropin. In one of the three guinea pigs who received testosterone, 2.5-cm bilateral cysts were grossly identified. Papillary excrescences were found on the ovarian surface in four guinea pigs, three who received testosterone and one who received megestrol. The proliferating epithelial cells also formed benign glands in the ovarian stroma in two guinea pigs who received testosterone, the most exuberant epithelial proliferations, including large bilateral cystadenomas, papillary excrescence that formed a small papillary neoplasm, and glands in the ovarian stroma that formed adenomatous areas, were seen in the guinea pig who received an intermediate dose of testosterone for the longest time. By radioimmunoassay, the serum level of testosterone was 22 ng/dL in one of the controls and 10,000, 12,000, and 15,000 ng/dL in the three guinea pigs who received testosterone. In the guinea pig with the most exuberant epithelial proliferation, the level of testosterone in the uterus was similar to that in the serum (13,860 ng/mg), but in the wall of the ovarian epithelial cyst, it was three times higher than it was in the serum (44,000 ng/mg). Our study shows that testosterone stimulates the growth of epithelial cells in the ovaries of guinea pigs, resulting in benign cysts, small adenomas in the ovarian parenchyma, and papillomas on the ovarian surface. The study also shows that guinea pigs can be used as an animal model for epithelial tumors of the human ovary.

We have characterized the folate receptor in malignant and benign tissues of human female genital tract (Fallopian tube and benign and malignant tissues of uterus). Radioligand binding displayed characteristics similar to those of other folate binding proteins. Those include a high-affinity type of binding (K = 10(10)M-1), apparent positive cooperativity, a slow dissociation at pH 7.4 becoming rapid at pH 3.5, and inhibition of binding by folate analogues. The gel filtration profile of Triton X-100 solubilized tissue contained two large peaks of 3H-folate labelled protein (> = 130 and 100 kDa) as well as a 25 kDa peak. Only a single band of 70 kDa was seen on SDS-PAGE immunoblotting. The large molecular size forms on gel filtration appear to represent folate receptors having a hydrophobic membrane anchor inserted into Triton X-100 micelles. The folate receptor of female genital tract showed cross-reactivity in ELISA and positive immunostaining with rabbit antibodies against human milk folate binding protein. Variations in the ratio of immunoresponse to total high affinity folic acid binding suggests the presence of multiple isoforms of the receptor in different types of malignant and benign tissues.

Ovarian cysts are detected in female patients of all ages. The patient's age, the size of the cyst, and the ultrasound appearance are helpful in determining which ovarian cysts necessitate observation and which necessitate surgical excision. The cancer antigen 125 level alone does not help to distinguish between benign and malignant ovarian cysts. The combination of benign findings on pelvic examination, a benign ultrasound appearance, and a cancer antigen 125 level within normal limits indicates a benign origin in practically all cases.

Radioimmunoassays of estradiol, CA125 and inhibin were carried out on ovarian cyst fluid samples. The samples were taken from ten women with functional cysts and 15 women with organic cysts. Statistical analysis shows that estradiol and inhibin assays allows satisfactory differential diagnosis between functional and organic cysts. However, the inhibin assay provides more precise results and appears to be a more reliable marker than estradiol. The differential diagnosis between the two types of cyst would indicate the use of coelioscopic surgery especially in the case of organic cysts, avoiding unnecessary risks for patients with functional cysts.

Background: The study was designed to improve the discrimination between functional and neoplastic ovarian cysts in order to avoid unnecessary surgery., Methods: Concentrations of tumor markers (CA 125, CEA, CASA, CA 72-4) and hormones (estradiol, FSH, LH) in cyst fluid were detected by enzyme immuno- or immunoradiometric assays. Wilcoxon test was used to evaluate the correlation of cyst fluid markers and histology., Results: One hundred and thirty-eight ovarian cyst aspirates were investigated. Seventy-one patients (51.5%) had functional cysts whereas 67 (48.5%) had benign (n=59) or malignant (n=8) cystic tumors. Statistically significant correlations of CA 125 (p<0.0005) and CASA (p<0.02) with neoplastic histology were found. No significant correlation could be detected between CA 72-4, CEA, or hormone values and histology. Elevated estradiol concentrations are suspicious for functional cysts in premenopausal age. Low FSH and LH levels seem to be an indicator for functional cysts in peri- and postmenopausal age., Conclusions: The assessed analytes could not reliably distinguish between functional and neoplastic ovarian cysts. Our results indicate that CA 125 is a marker for neoplastic histology in a proportion of ovarian cysts. The use of FSH and LH in the diagnosis of postmenopausal blastomas needs further investigation.

Composition and content of ceramides and gangliosides from different kinds of human ovary benign and malignant epithelial tumours were studied. The ceramide content was shown to decrease significantly in the tumours, especially in malignant tumours, in comparison with the normal ovary tissue. In the tumour ceramides a sphingosine base composition changes: sphinganine was found along with sphingenine, which is characteristic for normal ceramides. The fatty acid composition changes also. Main tumour gangliosides were shown to be GM3 and GD3. Their content decreases in malignant ovary tumours, especially the amount of ganglioside GD3. As a result of these changes the molar ratio Cer/Sia decreases. It can appears stimulates a tumour growth.

Studies on the structures and binding properties of the glycoproteins, purified from human ovarian cyst fluids, will aid the understanding of the carbohydrate alterations occurring during the biosynthesis of blood group antigens and neoplasm formation. These glycoproteins can also serve as important biological materials to study blood group A, B, H, Le(a), Le(b), Le(x), Le(y), T and Tn determinants, precursor type I and II sequences and cold agglutinin I and i epitopes. In this study, the binding property of a cyst glycoprotein from a human blood group Le(a+) nonsecretor individual, that contains an unusually high amount (18%) of sialic acid (HOC 350) was characterized by quantitative precipitin assay with a panel of lectins exhibiting a broad range of carbohydrate-binding specificities. Native HOC 350 reacted well only with three out of nineteen lectins tested. It precipitated about 80% of Ricinus communis (RCA1), 50% of Triticum vulgaris (WGA) and 37% of Bauhinia purpurea aba (BPA) agglutinins, respectively. However, its asialo product had dramatically enhanced reactivity and reacted well with many I/II (Gal beta1 --> 3/4GcNAc), T(Gal beta1 --> 3GalNAc) and Tn(GaNIAc alphaI --> Ser/Thr) active lectins. It bound best to Jacalin, BPA, and abrin-a and completely precipitated all the lectins added. Asialo-HOC 350 also reacted strongly with Wistaria floribunda, Abrus precatorius agglutinin, ricin and RCA1 and precipitated over 75% of the lectin nitrogen added, and moderately with Arachis hypogaea, Maclura pomifera, WGA, Vicia viosa-B4, Codium fragile tomentosoides and Ulex europaeus-II. But native HOC 350 and its asialo product reacted not at all or poorly with Dolichos biflorus, Helix pomatia, Lotus tetra-gonolobus, Ulex europaeus-I, Lens culinaris lectins and Con A. The lectin-glycoform interactions through bioactive sugars were confirmed by precipitin inhibition assay. Mapping the precipitation profiles of the interactions have led to the conclusion that HOC 350 contains a large number of receptors for I/II, T, and Tn active lectins. But in the untreated (or native) substance, most of these determinants are masked by sialic acids.

The expression of Ki-67 proliferation antigen and its relation to p53 protein was assessed immunohistochemically in malignant and benign ovarian neoplasms, considering the stage of disease and histology of tumors. The comparison of p53 and Ki-67 in tissue sections and respective cyst and/or ascitic fluid cells was also performed. Significant heterogeneity of staining was observed. However, the relationship between p53 and Ki-67 activity in tissue sections and loose cells in individual patients was evident. Moreover, the presence of Ki-67 antigen was closely correlated with p53 protein. It was observed the trend for serous carcinoma to have a higher Ki-67 and p53 positivity versus endometrioid and mucinous carcinomas. However, it was not statistically significant. Both growth fraction as measured by Ki-67 staining and p53 content were significantly higher in stages III and IV compared to stages I and II of ovarian carcinomas (P<.05, and P<.01, respectively). In benign ovarian neoplasms, no p53 reactivity was observed and Ki-67 staining was very low. Our results showed that p53 is not a feature of benign epithelial ovarian tumors and indicate that increased proliferative activity of cells seems to involve immunohistochemically detectable alterations in p53 gene contributing to the evolution of ovarian carcinoma.