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We determined whether the mutations found in ovarian cancers could be identified in the patients' ovarian cyst fluids. Tumor-specific mutations were detectable in the cyst fluids of 19 of 23 (83%) borderline tumors, 10 of 13 (77%) type I cancers, and 18 of 18 (100%) type II cancers. In contrast, no mutations were found in the cyst fluids of 18 patients with benign tumors or non-neoplastic cysts. Though large, prospective studies are needed to demonstrate the safety and clinical utility of this approach, our results suggest that the genetic evaluation of cyst fluids might be able to inform the management of the large number of women with these lesions.

Background: Mucins are heavily O-glycosylated proteins where the glycosylation has been shown to play an important role in cancer. Normal epithelial ovarian cells do not express secreted mucins, but their abnormal expression has previously been described in epithelial ovarian cancer and may relate to tumor formation and progression. The cyst fluids were shown to be a rich source for acidic glycoproteins. The study of these proteins can potentially lead to the identification of more effective biomarkers for ovarian cancer., Methods: In this study, we analyzed the expression of the MUC5AC and the O-glycosylation of acidic glycoproteins secreted into ovarian cyst fluids. The samples were obtained from patients with serous and mucinous ovarian tumors of different stages (benign, borderline, malignant) and grades. The O-linked oligosaccharides were released and analyzed by negative-ion graphitized carbon Liquid Chromatography (LC) coupled to Electrospray Ionization tandem Mass Spectrometry (ESI-MSn). The LC-ESI-MSn of the oligosaccharides from ovarian cyst fluids displayed differences in expression of fucose containing structures such as blood group ABO antigens and Lewis-type epitopes., Results: The obtained data showed that serous and mucinous benign adenomas, mucinous low malignant potential carcinomas (LMPs, borderline) and mucinous low-grade carcinomas have a high level of blood groups and Lewis type epitopes. In contrast, this type of fucosylated structures were low abundant in the high-grade mucinous carcinomas or in serous carcinomas. In addition, the ovarian tumors that showed a high level of expression of blood group antigens also revealed a strong reactivity towards the MUC5AC antibody. To visualize the differences between serous and mucinous ovarian tumors based on the O-glycosylation, a hierarchical cluster analysis was performed using mass spectrometry average compositions (MSAC)., Conclusion: Mucinous benign and LMPs along with mucinous low-grade carcinomas appear to be different from serous and high-grade mucinous carcinomas based on their O-glycan profiles.

Objective: The purpose of this study was to investigate cyst fluid levels of total iron, heme iron and free iron in benign endometriotic cysts and endometriosis-associated ovarian cancer (EAOC) and to demonstrate the significance of these biomarkers in differential diagnosis between EAOC and endometriotic cysts., Methods: Cyst fluid samples were obtained from eleven patients with EAOC and thirty-six women with benign endometriotic cysts at the time of surgery., Results: The median (± SD) total iron levels for endometriotic cysts and EAOC cysts were 244.4 ± 204.9 mg/L and 14.2 ± 36.6 mg/L, respectively. EAOC patients had much lower levels of iron-related compounds compared with endometriotic cyst samples (p< 0.001). When the total iron results were analyzed using the receiver operating characteristics (ROC) curve method, the optimum diagnostic cut-off point was 64.8 mg/L, sensitivity was 90.9%, specificity was 100%, positive predictive value (PPV) was 100%, and negative predictive value (NPV) was 97.3%. Patient demographic characteristics such as tumor size, age at operation, parity and menopause were not correlated with cyst fluid iron levels., Conclusions: We conclude for the first time that iron-related compounds are important biomarkers that can predict malignant transformation with high sensitivity and specificity for women with endometriosis.

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: Ovarian tumors, both benign and malignant, often contain cystic lesions. Analysis of cytokine levels of this enclosed fluid may be a pure way to study cytokine expression to gain more insight in tumor-host interaction., Methods: We analyzed the expression of cytokines in 45 cyst fluids from benign and malignant ovarian tumors and mapped the cytokine profiles for the different histological subgroups. The concentration of interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, interferon γ, tumor necrosis factor α, tumor necrosis factor β, transforming growth factor β, and C-C motif chemokine 22 was measured., Results: The presence of IL-6 in cyst fluid is correlated with malignancy. IL-8 was also expressed in benign samples, but the levels were significantly higher in malignant cyst fluids. Transforming growth factor β was only present in latent form in both benign and malignant cyst fluids. C-C motif chemokine 22 was detectable in higher levels in mucinous samples than in serous samples. IL-10 was not expressed in cyst fluid. T helper 1 subtype (TH1: IL-12 and IFN-γ) and TH2 (IL-4, IL-5) cytokines were similarly expressed in malignant and benign mucinous tumors. However, in the serous group, TH1 and TH2 cytokines were expressed in the benign samples but not in the malignant samples. In the high-grade malignant serous group, we found an inverse relationship between IL-8 levels and overall survival., Conclusions: Our results suggest that the immunosuppressive state created by ovarian cancer is reflected in the cystic fluid within the tumor. Furthermore, our findings suggest that type 1 and type 2 tumors have a distinct immunological profile and support the dualistic model for ovarian tumorigenesis.

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.

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.

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.

An imbalance between pro-angiogenic and anti-angiogenic factors is hypothesized in the pathogenesis of ovarian cystic disease. The aim of the following study was to explore the possible role of free vascular endothelial growth factor receptor 1 (sVEGFR-1), a soluble regulator of vascular endothelial growth factor (VEGF) action, in ovarian cystoadenoma, endometriomata and cystoadenocarcinoma. Forty-eight women, of whom fourteen had ovarian serous cysts, twenty-eight had stage III-IV ovarian endometriomata, and six had stage IIIB-IIIC ovarian carcinoma, were included. Sampling of serum, peritoneal and ovarian cystic fluids and of tumor tissue was performed before, during and following surgery, respectively. Levels of VEGF and sVEGFR-1 were measured in serum, peritoneal and cystic fluid. VEGF and sVEGFR-1 expression was evaluated in tumor tissue. There were no differences in serum VEGF and sVEGFR-1 levels nor in VEGF/VEGFR-1 ratio between study groups. Peritoneal fluid VEGF levels were higher in cystoadenocarcinoma patients than in endometriosis and in cystoadenoma patients, while sVEGFR-1 peritoneal fluid concentrations were significantly higher only in endometriosis-affected women. VEGF/VEGFR-1 ratio was highest in the peritoneal fluid of cancer patients with respect to the other two groups of women. Cystic fluid VEGF and VEGFR-1 concentrations were higher in endometriomata and in cystoadenocarcinomas than in cystadenomas but the VEGF/VEGFR-1 ratio was highest in cancer patients. Western blot evidenced a marked expression of VEGF and soluble VEGFR-1 in endometriosis tissue with respect to benign cyst tissue but a lower expression of both molecules, contrary to that expected, in cancer tissue. In conclusion, all in all, our data indicate that an excess of local VEGF with respect to its soluble receptor VEGFR-1 may be a key factor in the onset and maintenance of pathological neo-angiogenesis in ovarian cyst formation.

The objective of the present study was to determine the concentrations of LH, FSH, 17beta-estradiol and progesterone in ovarian cyst fluid and serum from patients with benign and malignant ovarian tumors and to assess the correlation of the gonadotropin and female sex steroid hormone concentrations with menopausal and tumor status. Ovarian cyst fluid and blood samples were prospectively collected from 103 patients with ovarian tumors. Seventy-four of the patients had benign ovarian tumors while 29 patients had malignant ovarian tumors. Malignant ovarian tumors showed significantly higher LH and FSH cyst fluid concentrations compared to concentrations from patients with benign tumors. Within the malignant subset, LH and FSH concentrations correlated with increasing FIGO stage and grade. Furthermore, LH and FSH cyst fluid concentrations showed strong correlations (r > 0.62) with serum concentrations in case of malignant tumors, especially in postmenopausal women, but not in case of benign tumors. The highest gonadotropin concentrations were observed in cyst fluid from malignant ovarian tumors. The most probable explanation for this is an increased vascular permeability within the cysts. Supportive evidence for such an increased vascular permeability is our previous finding of significantly higher VEGF concentrations in cyst fluid from malignant ovarian tumors. The possibility of ectopic production of LH and FSH by malignant ovarian tissue cannot completely be ruled out.

Objective: The soluble form of the vascular endothelial growth factor (VEGF) receptor, s-VEGFR-1, may negatively regulate the action of VEGF. Our purpose was to better understand the regulation of angiogenetic processes in ovarian cysts., Methods: Seventy-three women, 36 with serous cystoadenoma, 30 with ovarian endometriosis and seven with cystoadenocarcinoma, were enrolled. We calculated both VEGF and s-VEGFR-1 levels in cystic fluid and a VEGF activity index by means of the ratio VEGF/s-VEGFR-1. Student's t test was used for the statistical analysis., Results: We found higher VEGF concentration in both endometriotic and malignant lesions than in serous cystoadenoma (p=0.03 and 0.001, respectively). Also s-VEGFR-1 concentration was higher in endometrioma than in serous cysts (p=0.005); however, there was no statistically significant difference between cystoadenoma and the malignant lesions (p=0.15). VEGF activity index in cystoadenoma, endometriotic and malignant lesions was 0.61, 0.27 and 0.50, respectively., Conclusions: VEGF certainly has an important role in both ovarian endometriosis and for cancer progression; however, the activity index may be better to investigate the real role of VEGF in the pathology we have considered.

Objective: To describe the ultrasound and MR appearance of paraovarian cystadenomas., Methods: We reviewed retrospectively the radiologic findings in 7 patients with surgically proven paraovarian cystic neoplasms, including 6 serous cystadenomas and 1 borderline seromucinous cystadenoma. All had ultrasound and 4 had MR preoperatively., Results: On ultrasound, the ipsilateral ovary was visualized in six cases, in contact with the cyst in five and separate from it in one. On MR, the ovary and the cyst were visible in four cases, in contact in three and separate in one. Internal papillary excrescences, present at pathology in all cysts, were seen in five on ultrasound and in four on MR., Conclusion: Although the extraovarian location of these neoplasms is difficult to determine preoperatively by ultrasound and MR, these imaging modalities are more reliable in predicting the histology of these rare lesions and differentiating them from simple paraovarian cysts.

The aim of this work was to compare mean concentrations of gonadotropins in serum and fluid from malignant and benign ovarian tumors. We enrolled 126 patients diagnosed with malignant epithelial tumors (n=40), borderline epithelial tumors (n=14), benign cystadenomas (n=28) and simple cysts (n=44) of the ovary. Premenopausal and postmenopausal subgroups were formed in each group. The concentration of FSH and LH was measured in serum and tumor fluid and the serum/tumor fluid ratio was calculated. The results in each group were compared and the sensitivity, specificity, positive and negative predictive values were determined. Mean concentrations of both gonadotropins in ovarian cancer fluid were significantly higher than in the remaining groups (P ranged from <0.005 to <0.0001). Mean serum/fluid ratios were lowest in ovarian cancer (FSH=2.91, LH=4.19). Our findings support the hypothesis that gonadotropins are involved in ovarian carcinogenesis and suggest that gonadotropin serum/tumor fluid ratios could be of value in the differential diagnosis of functional and organic cysts of the ovary., (Copyright 2004 Society for Endocrinology)

Objective: The aim of this study was to define the role of luteinizing hormone (LH) as a tumor marker, specific for ovarian cancer., Methods: The study included 34 women with functional and benign ovarian cysts, 11 women with borderline ovarian tumors, 22 patients with advanced ovarian cancer and 15 patients with non-ovarian intraperitoneal malignancies. Serum, peritoneal fluid and ovarian cyst aspirates were obtained intraoperatively (laparoscopy or laparotomy) and were subjected to the LH analysis., Results: Peritoneal fluid LH levels were significantly increased in patients with ovarian cancer and those with borderline ovarian tumors as compared to patients with functional and benign ovarian cysts (P=0.005 and P=0.007, respectively). The patients with non-ovarian malignancies demonstrated the same peritoneal fluid LH levels as patients with benign ovarian tumors. There was no significant difference in the level of peritoneal fluid LH between ovarian cancer patients with and without ascites. The patients with functional and benign ovarian cysts demonstrated also significantly lower cyst fluid LH levels as compared to patients with malignant and borderline ovarian cysts (P=0.01 and P=0.03, respectively). Peritoneal and ovarian cyst fluid levels of LH were significantly increased in patients with fibrothecomas as compared to patients with other benign ovarian cysts. There were no significant differences in the serum LH levels comparing patients from all study groups., Conclusion: LH, detectable in peritoneal and ovarian cyst fluids, can be used as a tumor marker for identification of patients with borderline and malignant ovarian tumors.

Background: The serum markers CA125, tissue polypeptide specific antigen (TPS), and soluble interleukin-2 receptor alpha (sIL-2Ralpha) concentrations were determined in sera, cyst, and ascitic fluids from patients with malignant and benign ovarian neoplasms., Methods: CA125, TPS, and sIL-2Ralpha concentrations were measured in sera, cyst, and ascitic fluids by immunoassays in 67 patients with carcinoma and in 32 patients with benign ovarian neoplasms., Results: CA125, TPS, and sIL-2Ralpha levels were elevated significantly in sera from patients who had ovarian carcinoma compared with patients who had benign neoplasms (P < 0.001). Patients who had International Federation of Gynecology and Obstetrics (FIGO) Stage III-IV disease had significantly higher serum levels for the markers studied compared with patients who had FIGO Stage I-II disease (P < 0.001 for CA125; P = 0.02 for TPS and sIL-2Ralpha). Concurrent measurement of CA125 and sIL-2Ralpha in sera identified 100% of ovarian carcinomas in FIGO Stage I-II. All patients with carcinoma demonstrated markedly higher levels of CA125 and TPS for both cyst and ascites compared with corresponding sera (P < 0.001). The level of sIL-2Ralpha was higher statistically in ascitic fluid compared with the level in serum (P < 0.001); however, its values in sera and cyst fluids were comparable. In ascitic fluid, the CA125 level was significantly higher in patients who had FIGO Stage III-IV disease compared with patients who had FIGO Stage I-II disease (P = 0.002), whereas such correlations were not found for TPS or sIL-2Ralpha. In cyst fluids, the levels of all studied markers were independent of the FIGO stage. In cyst fluids from patients with benign ovarian neoplasms, TPS and sIL-2Ralpha levels were significantly lower compared with the levels in patients with ovarian carcinoma (P < 0.001), whereas the values of CA125 were overlapping. CA125 and TPS concentrations were higher in cyst fluids compared with corresponding sera, whereas sIL-2Ralpha levels were comparable and low in cyst fluids and in the circulation of patients with benign neoplasms., Conclusions: In patients with ovarian carcinoma, TPS and CA125 concentrations were significantly higher in the place of their generation compared with the concentrations in blood circulation. sIL-2Ralpha values were higher in ascites compared with the values in corresponding sera, and its concentrations in sera and cyst fluids were comparable. The assessment of serum sIL-2Ralpha levels showed potential complementary value to CA125 for the detection of ovarian carcinoma in early FIGO stages; however, a 9% false positive rate limited the significance of cumulative value for a combination of these circulating markers., (Copyright 2002 American Cancer Society.)

Background: Curschmann's spirals, first described more than 100 years ago, are common in cytologic specimens from the respiratory tract and have also been observed in cervical smears, urine, and peritoneal and pleural effusions. No simple theory can explain the exact mode of spiral formation, which is presumed to be a complex physical and biochemical phenomenon., Case: A 29-year-old woman, gravida 2, para 2, underwent right ovarian cyst excision after an abdominal ultrasound examination revealed a cystic mass of the right ovary. Histologically, the cyst was an immature cystic teratoma containing respiratory epithelium with mucous glands in the submucosa. Cytologic examination of the cyst fluid showed the presence of Curschmann's spirals., Conclusion: To the best of our knowledge, the formation of Curschmann's spirals associated with an immature cystic teratoma has not been previously reported. In this situation, the presence of spirals could be explained by formation from mucus normally found in that environment.

Objectives: Expression of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) in serous tumors of the ovary was investigated to determine whether and how these proteolytic enzymes are associated with the progression of these tumors., Methods: Cyst fluid of 24 serous ovarian tumors (8 adenocarcinomas, 2 borderline tumors and 14 adenomas) was analyzed using gelatin/casein zymography and enzyme-linked immunosorbent assay., Results: Concentrations of MMP-9 and MMP-2 were statistically higher in serous adenocarcinomas than in serous adenomas (p < 0.01, p < 0.05, respectively), while the concentrations of TIMP-1 and TIMP-2 showed no significant difference between adenocarcinomas and adenomas. The molar ratio of TIMP-2/MMP-2 was lower in adenocarcinomas than in adenomas (p < 0.05). With gelatin zymography, the MMP-9 band was detected in all serous adenocarcinomas, but only in 8 of 14 serous adenomas (p = 0.05). Using casein zymography, MMP-7 was more frequently detected in serous adenocarcinomas (7/8) than in serous adenomas (4/14; p < 0.05)., Conclusions: These observations indicate that matriolytic enzymes such as MMP-2, MMP-7 and MMP-9 are secreted into cyst fluid from serous adenocarcinoma tissues. In part, the aggressive invasion of serous carcinoma cells may be explained by the expression of matriolytic enzymes., (Copyright 2001 S. Karger AG, Basel)

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.