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Ovarian Tumors (ovarian + tumor)
Kinds of Ovarian Tumors Selected AbstractsMetastatic "Borderline" Papillary Ovarian Tumor in an Intramammary Lymph NodeTHE BREAST JOURNAL, Issue 5 2002André L. Moreira MD No abstract is available for this article. [source] Molecular classification of borderline ovarian tumors using hierarchical cluster analysis of protein expression profilesINTERNATIONAL JOURNAL OF CANCER, Issue 6 2002Ayodele A. Alaiya Abstract Ovarian tumors range from benign to aggressive malignant tumors, including an intermediate class referred to as borderline carcinoma. The prognosis of the disease is strongly dependent on tumor classification, where patients with borderline tumors have much better prognosis than patients with carcinomas. We here describe the use of hierarchical clustering analysis of quantitative protein expression data for classification of this type of tumor. An accurate classification was not achieved using an unselected set of 1,584 protein spots for clustering analysis. Different approaches were used to select spots that were differentially expressed between tumors of different malignant potential and to use these sets of spots for classification. When sets of proteins were selected that differentiated benign and malignant tumors, borderline tumors clustered in the benign group. This is consistent with the biologic properties of these tumors. Our results indicate that hierarchical clustering analysis is a useful approach for analysis of protein profiles and show that this approach can be used for differential diagnosis of ovarian carcinomas and borderline tumors. © 2002 Wiley-Liss, Inc. [source] Evaluation of cases where the right kidney is higher than the left kidneyINTERNATIONAL JOURNAL OF UROLOGY, Issue 7 2003SEIICHI SAITO Abstract Background: Finding the right kidney higher than the left kidney on excretory urography (EXU) is unusual. In the present study, the position of the kidneys was evaluated in patients, and the frequency, causes or attribution were investigated. Methods: Kidney positions were evaluated in 1625 patients. Subsequent evaluations by computed tomography scan were performed for each case where the right kidney was higher than the left. If a patient had right hydronephrosis, bladder evaluations such as ultrasonography and/or cystoscopy were also conducted. Patients with a left contracted kidney were excluded. Results: The right kidney was higher than the left in 81 (5%) of 1625 cases. In 30 cases (37%), the cause or attribution existed in the right urinary tract. Eleven of these cases were due to tumors or cysts in the right kidney, four were due to congenital anomalies, and 15 were due to hydronephrosis. In 10 (12.3%) of the cases, the cause or attribution existed in the left urinary tract. All of them were cysts or tumors of the left kidney. Of the other 13 (16.0%) cases, eight were caused by hepatatrophy and splenomegaly as a result of liver cirrhosis, two were caused by aortic aneurysm, one was caused by visceral inversion, one was caused by a right ovarian tumor, and one was caused by pneumonectomy. Malignancies, including two renal cell carcinomas and three bladder cancers at the right ureteral orifice, were found in five cases (6%). Conclusion: The above results suggest that the right kidney is higher than the left in five percent of all cases undergoing EXU. In cases where the right kidney is higher than the left, and a left contracted kidney cannot be found, further evaluation is recommend. [source] Preoperative evaluation and triage of women with suspicious adnexal masses using risk of malignancy indexJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 1 2009Christopher A. Enakpene Abstract Aims:, To test the accuracy of risk of malignancy index (RMI) in preoperative prediction of malignancy and treatment of adnexal masses. Methods:, A total of 302 women with ultrasound diagnosed adnexal masses, and serum measurement of cancer-associated antigen CA-125 levels, were studied. They all had surgical exploration between October 2001 and September 2005 at the Friedrich-Alexander University Women's Hospital, Erlangen, Germany. The RMI was based on menopausal status, ultrasound morphology of adnexal masses and absolute level of serum CA-125. A cut-off of 250 was chosen as the threshold for determining the type of surgical operations (laparotomy versus laparoscopy) and the skill of the surgeons (gynecological oncologist versus general gynecologist). The data obtained were analyzed for baseline characteristics using ,2 test and analysis of variance (ANOVA). P < 0.05 were statistically significant. The various testing methods were evaluated for sensitivity, specificity, positive and negative predictive values. Results:, The best individual performance was found in RMI at a cut-off of 250 with a sensitivity of 88.2%, specificity of 74.3%, positive predictive value of 71.3% and negative predictive value of 90%. When RMI was used to triage patient treatment, 81.5% of patients who had laparoscopy had histological diagnosis of benign ovarian tumor and 7.5% had malignant tumor. In contrast, 74.4% of patients who had laparotomy had histological diagnosis of malignant ovarian tumor and 16% had benign tumor. Conclusion:, Risk of malignant index is a reliable, cheap, readily available and cost-effective method of preoperative discrimination of benign from malignant adnexal masses. It is also helpful in triaging patients to different treatment groups. [source] Virilization in pregnancy due to a borderline mucinous ovarian tumorJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2007Selvan Pather Abstract Virilization in pregnancy due to borderline mucinous ovarian tumors is very rare. A case of a 28-year-old patient who was noted at 28 weeks' gestation to have marked virilization with raised serum androgens, ascites and a large complex right adnexal mass is presented. Delivery was carried out by cesarean section and at surgery a large tumor was noted in the right ovary. Histology revealed a borderline mucinous ovarian tumor with stromal luteinization, but there was no evidence of stromal invasion. Serum androgens returned to normal levels following surgery and the maternal virilization had resolved at the 6-week postnatal visit. Stromal changes in borderline mucinous ovarian tumors may result in virilization due to androgen production; surgical removal is associated with an excellent clinical outcome. [source] A case of pulmonary type of ovarian small cell carcinomaJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 2 2007Nao Suzuki Abstract Small cell carcinoma is a rare form of ovarian cancer with a poor prognosis. It is divided into two types, the hypercalcemic and the pulmonary type, of which the latter is extremely rare. A 49-year-old woman presented with an acute abdomen and was suspected to have torsion of a left ovarian tumor, which was followed up with an emergency operation. Postoperative pathological examination gave a diagnosis of the pulmonary type of ovarian small cell carcinoma. Six courses of paclitaxel and carboplatin therapy were given as adjuvant chemotherapy. The patient has survived for 36 months without recurrence. Here we present an extremely rare patient with the pulmonary type of ovarian small cell carcinoma. [source] Preoperative plasma osteopontin level as a biomarker complementary to carbohydrate antigen 125 in predicting ovarian cancerJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2006Mitsuhiro Nakae Abstract Aim:, New biomarkers other than carbohydrate antigen (CA) 125 are needed for the detection of ovarian cancer. Osteopontin (OPN) is one of the candidates identified by high-throughput complementary DNA microarray techniques. We evaluated the preoperative plasma OPN level as a diagnostic biomarker for ovarian cancer in comparison with CA125. Methods:, Preoperative plasma OPN and CA125 levels were measured and compared in 32 patients with ovarian cancer, 34 patients with benign ovarian tumor, 30 patients with other gynecologic cancers and 31 healthy women. Preoperative plasma OPN levels were also assessed according to tumor stage, the volume of ascites and histological types. The sensitivity and specificity for predicting ovarian cancer was compared between OPN and CA125. Results:, Preoperative plasma OPN levels were significantly higher in patients with ovarian cancer than in those with benign ovarian tumor, in other gynecologic patients or in healthy women. Stage IV ovarian cancer patients and ovarian cancer patients with ascites had higher plasma OPN levels than those without ascites and in a lower stage. There was no relation between OPN and the histological type. The sensitivity of preoperative plasma OPN in detecting ovarian cancer was 81.3% and almost reached that of CA125. The specificity was moderate. Sensitivity increased to 93.8% with the combination of CA125, compared to 84.4% with CA125 alone. Conclusion:, Preoperative OPN is a useful biomarker for predicting ovarian cancer. It is especially useful when used complementary to CA125. Larger studies of patients with ovarian cancer showing a low CA125 level or in early stages of ovarian cancer are needed. [source] Accuracy of frozen section in the diagnosis of malignant ovarian tumorJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 5 2004Dittakarn Boriboonhirunsarn Abstract Aim:, To evaluate the diagnostic accuracy of frozen section for histopathologic diagnosis of ovarian tumors. Methods:, A total of 147 surgically removed ovarian tumors were studied. Each ovarian tumor sample was evaluated for histopathologic diagnosis using both frozen and paraffin sections. Interpretation was separate and blinded between each technique. Accuracy, diagnostic values and their 95% confidence intervals (CI) were estimated by comparing the results from both techniques, using paraffin section as a gold standard. Results:, Overall accuracy of frozen section was 89.8% (95% CI 83.4,94.0). Sensitivity was 90.4% (95% CI 78.2,96.4) for malignant, 33.3% (95% CI 6.0,75.9) for borderline, and 93.3% (95% CI 85.4,97.2) for benign tumors. The predictive value was 100% (95% CI 90.6,100) for malignant, 20% (95% CI 3.5,55.8) for borderline, and 92.2% (95% CI 84.1,96.5) for benign tumors. Most false negatives occurred in mucinous and borderline tumors. No benign tumor was misdiagnosed as malignant by frozen section. Accuracy and negative predictive value were significantly lower in epithelial rather than germ and other cell types. Excellent agreement with regard to histologic cell type was observed (Kappa 0.81). Conclusion:, Frozen section appears to be an accurate technique for the histopathologic diagnosis of ovarian tumors. Some limitations were observed among borderline and mucinous tumors; this emphasizes the great value of frozen section in the diagnosis of ovarian tumors. [source] Ovarian endodermal sinus tumor in a 76-year-old womanJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 5 2003Gülaydan Filiz Abstract A 76-year-old woman underwent surgery for pelvic mass, during which a 13 × 8-cm right ovarian tumor was discovered. On histopathological examination, she was diagnosed with an endodermal sinus tumor with right tubal metastasis. The patient was treated with four cycles of Bleomycin, Etoposide and Cisplatin. She died of disseminated disease four years later. [source] Increased staining for phosphorylated AKT and nuclear factor-,B p65 and their relationship with prognosis in epithelial ovarian cancerPATHOLOGY INTERNATIONAL, Issue 12 2008Rui-Xia Guo AKT plays an important role in malignant behavior of tumors. The purpose of the present study was to determine the expression of phosphorylated AKT (P-AKT) and nuclear factor-,B (NF-,B) p65 and their association with clinicopathological parameters and prognosis in epithelial ovarian tumor. On immunohistochemistry 115 samples of ovarian tissue that included 68 specimens of epithelial ovarian cancer, 12 of borderline tumor, 24 of epithelial benign tumor and 11 of normal ovary, were evaluated. Sixty-three patients with ovarian cancer were followed up from 7 to 68 months. The positive expression rate of P-AKT and NF-,B p65 were higher in epithelial ovarian cancer than in normal ovarian tissue (P < 0.01). Elevated P-AKT or NF-,B p65 expression was significantly correlated with late clinical stage (P < 0.05 and P < 0.01) and poor histological differentiation (both P < 0.01). P-AKT expression was significantly correlated with NF-,B p65 immunostaining (, = 0.272, P < 0.05). Elevated expression of P-AKT was negatively correlated with the survival of ovarian cancer patients, but it was not an independent prognostic factor after multivariate analysis. Overexpression of P-AKT and NF-,B p65 were involved in the carcinogenesis and metastasis of ovarian cancer. P-AKT might contribute to the malignant transformation through NF-,Bp65 upregulation. [source] Adenosarcoma of the uterine corpus associated with ovarian thecomaPATHOLOGY INTERNATIONAL, Issue 9 2001Kouichi Nomura We describe a case of adenosarcoma of the uterine corpus associated with ovarian thecoma in a 67-year-old woman. The patient underwent surgery under a diagnosis of ovarian carcinoma. The 110 × 70 mm-sized ovarian tumor was diagnosed as thecoma. The polypoid tumor of the uterine corpus which measured 30 × 15 mm was diagnosed as adenosarcoma. Cells of both epithelial and stromal elements of the adenosarcoma expressed estrogen receptors (determined by immunohistochemistry). These findings support the view that estrogen stimulation, including that by a pre-existing ovarian thecoma, may play a role in the development of mesenchymal and mixed epithelial / mesenchymal uterine tumors, including adenosarcoma. [source] Efficacy and safety of linezolid in immunocompromised children with cancerPEDIATRICS INTERNATIONAL, Issue 5 2010Maria Moschovi Abstract Background:, The aim of this study was to determine the safety, tolerance and efficacy of linezolid for the treatment of infections from Gram-positive bacteria in immunocompromised children with cancer. Methods:, This was a prospective non-comparative unblinded study in the Hematology/Oncology Unit over a two-year period, administering linezolid as monotherapy in children with cancer. Results:, Seventeen children received linezolid (30 mg/kgr: 3 i.v. per day). Mean duration of linezolid administration was 12.2 days (range, 6,38 days), while the median age of the evaluable patients was 2.2 years (range, 6 months,11.2 years). Primary diagnosis was acute lymphoblastic leukemia (nine patients), brain tumor (three patients), multi-organ Langerhans cell histiocytosis (two patients), rhabdomyosarcoma, Burkitt's lymphoma and ovarian tumor (one patient each). All patients were in the midst of chemotherapy cycles. Ten out of 17 children had positive blood cultures (methicillin-resistant Staphylococcus aureus, four patients; vancomycin-resistant Enterococcus, three patients; penicillin-resistant Streptococcus pneumoniae, three patients), while seven of the 17 had fever and vancomycin-resistant Enterococcus in stool cultures. All patients were considered clinically cured after the end of the linezolid regimen (100% efficacy). The main adverse events were thrombocytopenia grade 1,3 and anemia grade 2,3 (four and two patients, respectively). Chemotherapy-induced myelotoxicity (six patients) was not worsened during linezolid therapy. No bleeding episodes were presented. Self-limited diarrhea grade 1,2 was presented in four patients (mean duration 2 days). The total adverse event rate was 23.5%; however, there was no premature cessation of linezolid in any patient. Conclusions:, Linezolid may be another effective and safe therapy to treat infections from resistant Gram-positive bacteria in immunocompromised children, even in young ages. [source] Limited prognostic value of tissue protein expression levels of BCl-2 in Danish ovarian cancer patients: from the Danish ,MALOVA' ovarian cancer studyAPMIS, Issue 8 2010ESTRID V.S. Høgdall Høgdall EVS, Christensen L, Kjaer SK, Blaakaer J, Christensen IJ, Høgdall CK. Limited prognostic value of tissue protein expression levels of BCl-2 in Danish ovarian cancer patients. APMIS 2010; 118: 557,64. The purpose of the study was to determine the expression of BCl-2 in epithelial ovarian tumors and to correlate expression levels with selected clinicopathologic parameters, time to progression and prognosis of the disease. Using tissue arrays (TA), we analyzed BCl-2 expression in tissues from 191 women diagnosed with low malignant potential ovarian tumors (LMP) and from 582 patients diagnosed with ovarian cancer (OC). Using 30% as cutoff level for BCl-2 overexpression, 5% of LMPs were positive with a higher proportion of serous ovarian tumor of LMP, compared to mucinous ovarian tumor of LMP (p = 0.02). Women with a BCl-2-positive LMP tumor were older than women with a BCl-2 negative tumor (p = 0.02). Ten percent of OCs were positive for BCl-2 expression (,30%). No significant association was found between BCl-2 expression levels and histologic type of tumors (serous vs mucinous, p = 0.19). A 30% cutoff value or a percentage scale showed that BCl-2 expression had no prognostic value, both in univariate and in multivariate survival analyses. No difference in time to progression was observed between patients with BCl-2-positive and negative tumors. These data suggest that BCl-2 expression may not be of important clinical value in the treatment of Danish OC patients. [source] Psammoma bodies in cervical smear in association with keratinizing squamous cell carcinoma of cervix: A case reportDIAGNOSTIC CYTOPATHOLOGY, Issue 6 2009K. Raveendran Pillai Ph.D. Abstract The presence of psammoma bodies (PBs) in cervical smears is a rare finding. These structures have been identified in association with a wide range of benign and malignant conditions within the female genital tract. PBs in cervical smears have usually been associated with malignant serous epithelial ovarian tumors. However, many PBs associated with atypical squamous cells were detected in cervical smears of an 83-year-old woman with complaint of postmenopausal bleeding. Colposcopic examination revealed an ulceroinfiltrative growth in the cervix. Histological examination of the biopsy specimen from the growth revealed keratinizing squamous cell carcinoma with multiple and singly arranged PBs. This report suggests that cytologists should aware of the possibilities, on finding PBs associated with atypical cells in cervical specimens and report the cases accordingly. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] Clear-cell adenocarcinoma of the female genital tract: Presence of Hyaline stroma and tigroid background in various types of cytologic specimensDIAGNOSTIC CYTOPATHOLOGY, Issue 6 2005Surapan Khunamornpong M.D. Abstract Hyaline basement membrane-like stromal material and tigroid background are distinctive cytologic features observed in Diff-Quik (DQ)- or Giemsa-stained smears of clear-cell adenocarcinoma (CCA) of the female genital tract. However, it is uncertain how often these features are present in different types of cytologic specimens, and which type of preparation is optimal for this diagnosis. We therefore reviewed the cytologic features of CCA in three types of specimens, including 15 scrape cytology specimens, 7 fine-needle aspiration (FNA) specimens, and 15 peritoneal cytology specimens, with emphasis on the features observed in DQ-stained smears. The cell morphology in scrape cytology specimens and FNA specimens was comparable, whereas in peritoneal cytology specimens, the cytoplasm was better preserved. Most tumor cells had fragile cytoplasm containing variable amounts of fine vacuoles, and round nuclei with distinct or prominent nucleoli. Hyaline stroma was present in 93% of scrape cytology specimens, 71% of FNA specimens, and 80% of peritoneal cytology specimens. Tigroid background was observed in 47% of scrape cytology specimens, 43% of FNA specimens, but in none of the peritoneal cytology specimens. Formation of a tigroid background may be prevented by the abundant fluid content in peritoneal cytology specimens. Hyaline stroma and tigroid background were uncommonly seen in scrape smears from other types of primary ovarian tumors, mainly juvenile granulosa cell tumor and yolk sac tumor. However, the additional presence of papillary structures allows CCA to be readily distinguished from these other tumors. We propose that scrape cytology offers the best approach for the intraoperative cytologic diagnosis of CCA. Diagn. Cytopathol. 2005;32:336,340.© 2005 Wiley-Liss, Inc. [source] Atypical papillary proliferation in gynecologic patients: A study of 32 pelvic washes,DIAGNOSTIC CYTOPATHOLOGY, Issue 2 2005Karyna C. Ventura M.D. Abstract Papillary clusters in gynecologic pelvic washes frequently cause diagnostic challenges because they can be associated with borderline or malignant ovarian tumors, as well as benign pelvic diseases. The objective of our study was to review all pelvic washes with atypical papillary proliferation (APP) and investigate whether cytomorphology and/or immunohistochemistry on cell block could determine their origin. Thirty-two pelvic washes from 31 patients containing APP were reviewed and correlated with their corresponding gynecologic or pelvic disease. Previously obtained cell blocks with immunohistochemical (IHC) stains were reviewed also. Nine of 32 washes (28%) were overcalled as malignant and were from patients with 5 borderline serous ovarian tumors (BSTO), 1 ovarian follicular cyst, 1 serous cystadenofibroma, and 1 endometrial carcinoma with ovarian seromucinous cystadenoma. BSTO and endometriosis were the most common sources of APP. Cell blocks could not discriminate further the etiology of APP. Immunohistochemistry was performed rarely and not fully contributory. Caution in interpreting papillary groups and cytohistological correlation is recommended to prevent a high false positive rate. Diagn. Cytopathol. 2005;32:76,81. © 2005 Wiley-Liss, Inc. [source] Analysis of chromosomal changes in serous ovarian carcinoma using high-resolution array comparative genomic hybridization: Potential predictive markers of chemoresistant diseaseGENES, CHROMOSOMES AND CANCER, Issue 1 2007Sang Wun Kim The mechanism of drug resistance in cancer is multifactorial, and the accumulation of multiple genetic changes may lead to drug-resistant phenotypes. This study sought to determine characteristic genetic changes in chemoresistant serous ovarian carcinomas using high-resolution array comparative genomic hybridization (aCGH), and identified genomic aberrations that could be used as predictive markers of chemoresistant disease. Seventeen primary ovarian tumors from optimally debulked stage IIIc serous ovarian carcinoma patients were analyzed using aCGH. Ten patients had chemoresistant disease (progression within 12 months of initial chemotherapy), whereas seven patients had chemosensitive disease (no recurrence for more than 36 months). Receiver operating characteristics curve analysis was used to select chromosomal aberrations that could help distinguish chemoresistant disease from chemosensitive disease. In 17 tumors, frequent increases in DNA copy number were seen on 1p36.33, 3q26.2, 8q24.3, 10q26.3, 12p11.21, 20q13.33, and 21q22.3, and frequent losses were observed on 4p12, 5q13.2, 7q11.21, 8p23.1, 14q32.33, Xq13.3, and Xq21.31. The gains on 5p15.33 and 14q11.2, and losses on 4q34.2, 4q35.2, 5q15, 8p21.1, 8p21.2, 11p15.5, 13q14.13, 13q14.2, 13q32.1, 13q34, 16q22.2, 17p11.2, 17p12, and 22q12.3 were more frequent in chemoresistant disease. The losses on 13q32.1 and 8p21.1 had the largest areas under the curve (AUC 0.90 and 0.85, respectively). The most reliable combination of chromosomal aberrations for detecting chemoresistant disease was the loss on 13q32.1 and 8p21.1 (AUC 0.950). Our findings suggest that these chromosomal aberrations are potential predictive markers of chemoresistant disease in patients with serous ovarian carcinomas. © 2006 Wiley-Liss, Inc. [source] Type-specific roles of histone deacetylase (HDAC) overexpression in ovarian carcinoma: HDAC1 enhances cell proliferation and HDAC3 stimulates cell migration with downregulation of E-cadherinINTERNATIONAL JOURNAL OF CANCER, Issue 6 2010Akiko Hayashi Abstract Histone acetylation/deacetylation controls chromatin activity and subsequent gene transcription. Recent studies demonstrated the activation of histone deacetylases (HDACs) in various human malignancies; however, the expression and function of HDACs in ovarian tumors are not fully understood. In this study, we examined the immunohistochemical expression of HDAC1, HDAC2 and HDAC3 using tissues obtained from 115 cases of ovarian tumors and compared it with that of Ki-67 (a growth marker), p21, and E-cadherin and clinicopathological parameters. In addition, we analyzed the effect of specific siRNA for HDAC1, HDAC2 and HDAC3 on the expression of cell cycle-related molecules and E-cadherin to clarify the functional difference among the 3 HDACs. The results indicated that the immunohistochemical expression of nuclear HDAC1, HDAC2 and HDAC3 proteins increased stepwise in benign, borderline and malignant tumors. The expression of HDAC1 and HDAC2 was correlated with Ki-67 expression and that of HDAC3 was inversely correlated with E-cadherin expression. Among the HDACs examined, only HDAC1 was associated with a poor outcome, when overexpressed. Treatment with HDAC inhibitors suppressed the proliferation of ovarian cancer cells in association with apoptosis. A specific siRNA for HDAC1 significantly reduced the proliferation of ovarian carcinoma cells via downregulation of cyclin A expression, but siRNA for HDAC3 reduced the cell migration with elevated E-cadherin expression. Our results suggested that HDAC1 plays an important role in the proliferation of ovarian cancer cells, whereas HDAC3 functions in cell adhesion and migration. Therefore, specific therapeutic approaches should be considered according to the HDAC subtypes. [source] Expression profiling correlates with treatment response in women with advanced serous epithelial ovarian cancerINTERNATIONAL JOURNAL OF CANCER, Issue 4 2006Tanya R. Newton Abstract The majority of epithelial ovarian carcinomas are of serous subtype, with most women presenting at an advanced stage. Approximately 70% respond to initial chemotherapy but eventually relapse. We aimed to find markers of treatment response that might be suitable for routine use, using the gene expression profile of tumor tissue. Thirty one women with histologically-confirmed late-stage serous ovarian cancer were classified into 3 groups based on response to treatment (nonresponders, responders with relapse less than 12 months and responders with no relapse within 12 months). Gene expression profiles of these specimens were analyzed with respect to treatment response and survival (minimum 36 months follow-up). Patients' clinical features did not correlate with prognosis, or with specific gene expression patterns of their tumors. However women who did not respond to treatment could be distinguished from those who responded with no relapse within 12 months based on 34 gene transcripts (p < 0.02). Poor prognosis was associated with high expression of inhibitor of differentiation-2 (ID2) (p = 0.001). High expression of decorin (DCN) and ID2 together was strongly associated with reduced survival (p = 0.003), with an estimated 7-fold increased risk of dying (95% CI 1.9,29.6; 14 months survival) compared with low expression (44 months). Immunohistochemical analysis revealed both nuclear and cytoplasmic distribution of ID2 in ovarian tumors. High percentage of nuclear staining was associated with poor survival, although not statistically significantly. In conclusion, elevated expression of ID2 and DCN was significantly associated with poor prognosis in a homogeneous group of ovarian cancer patients for whom survival could not be predicted from clinical factors. © 2006 Wiley-Liss, Inc. [source] High tumor tissue concentration of urokinase plasminogen activator receptor is associated with good prognosis in patients with ovarian cancerINTERNATIONAL JOURNAL OF CANCER, Issue 4 2003Christer Borgfeldt Abstract The urokinase plasminogen activator (uPA) system is involved in tumor growth and metastasis. We assayed the components of the uPA system in homogenates of 64 primary epithelial ovarian tumors and 5 metastases and evaluated the association of these parameters to prognosis in the 51 malignant cases. The levels of uPA, PAI-2 and the uPA:PAI-1 complex increased with progressive loss of histological differentiation (ptrend <0.001, <0.05 and <0.001). The level of PAI-1 was higher in poorly than in well/moderately differentiated tumors (p = 0.03). The content of uPAR was lower in benign tumors as compared to borderline malignancies (p = 0.002), invasive primary tumors (p < 0.001), and metastases (p = 0.002). Surprisingly, the level of uPAR was lower in poorly differentiated as compared to both borderline (p = 0.01) and well differentiated malignant tumors (p = 0.005). Also, the level of uPAR was lower in advanced as compared to early stages of the disease (ptrend = 0.002). The median follow-up time for patients was 5.8 years. High tumor tissue levels of uPAR were associated with longer postoperative survival (HR = 0.4, 95% CI = 0.2,0.8, p = 0.01). In contrast, shorter survival was evident in patients with high tumor levels of uPA from 2 years on after operation (HR = 4.6, 95% CI = 1.2,17, p = 0.02). High tPA levels tended to be associated with shorter overall survival after 2 years (HR = 2.9, 95% 95% CI = 0.9,9.8, p = 0.08). Although high tumor tissue content of uPAR was associated with a less aggressive phenotype characterized by well differentiated histology and longer survival, low content of uPAR in the poorly differentiated tumors and metastases presumably results from increased elimination of uPAR. © 2003 Wiley-Liss, Inc. [source] Molecular classification of borderline ovarian tumors using hierarchical cluster analysis of protein expression profilesINTERNATIONAL JOURNAL OF CANCER, Issue 6 2002Ayodele A. Alaiya Abstract Ovarian tumors range from benign to aggressive malignant tumors, including an intermediate class referred to as borderline carcinoma. The prognosis of the disease is strongly dependent on tumor classification, where patients with borderline tumors have much better prognosis than patients with carcinomas. We here describe the use of hierarchical clustering analysis of quantitative protein expression data for classification of this type of tumor. An accurate classification was not achieved using an unselected set of 1,584 protein spots for clustering analysis. Different approaches were used to select spots that were differentially expressed between tumors of different malignant potential and to use these sets of spots for classification. When sets of proteins were selected that differentiated benign and malignant tumors, borderline tumors clustered in the benign group. This is consistent with the biologic properties of these tumors. Our results indicate that hierarchical clustering analysis is a useful approach for analysis of protein profiles and show that this approach can be used for differential diagnosis of ovarian carcinomas and borderline tumors. © 2002 Wiley-Liss, Inc. [source] Combinatorial Modification of Degradable Polymers Enables Transfection of Human Cells Comparable to Adenovirus,ADVANCED MATERIALS, Issue 19 2007J. Green End-modified poly(,-amino ester)s, easy-to-synthesize degradable polymers, are able to deliver DNA to primary human cells at levels comparable to adenovirus and two orders of magnitude better than the commonly used non-viral vector, polyethylenimine. Small structural changes are found to affect multiple steps of gene delivery including the DNA binding affinity, nanoparticle size, intracellular DNA uptake, and final protein expression. In vivo, these polymer modifications enhance DNA delivery to ovarian tumors. [source] Virilization in pregnancy due to a borderline mucinous ovarian tumorJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2007Selvan Pather Abstract Virilization in pregnancy due to borderline mucinous ovarian tumors is very rare. A case of a 28-year-old patient who was noted at 28 weeks' gestation to have marked virilization with raised serum androgens, ascites and a large complex right adnexal mass is presented. Delivery was carried out by cesarean section and at surgery a large tumor was noted in the right ovary. Histology revealed a borderline mucinous ovarian tumor with stromal luteinization, but there was no evidence of stromal invasion. Serum androgens returned to normal levels following surgery and the maternal virilization had resolved at the 6-week postnatal visit. Stromal changes in borderline mucinous ovarian tumors may result in virilization due to androgen production; surgical removal is associated with an excellent clinical outcome. [source] Accuracy of frozen section in the diagnosis of malignant ovarian tumorJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 5 2004Dittakarn Boriboonhirunsarn Abstract Aim:, To evaluate the diagnostic accuracy of frozen section for histopathologic diagnosis of ovarian tumors. Methods:, A total of 147 surgically removed ovarian tumors were studied. Each ovarian tumor sample was evaluated for histopathologic diagnosis using both frozen and paraffin sections. Interpretation was separate and blinded between each technique. Accuracy, diagnostic values and their 95% confidence intervals (CI) were estimated by comparing the results from both techniques, using paraffin section as a gold standard. Results:, Overall accuracy of frozen section was 89.8% (95% CI 83.4,94.0). Sensitivity was 90.4% (95% CI 78.2,96.4) for malignant, 33.3% (95% CI 6.0,75.9) for borderline, and 93.3% (95% CI 85.4,97.2) for benign tumors. The predictive value was 100% (95% CI 90.6,100) for malignant, 20% (95% CI 3.5,55.8) for borderline, and 92.2% (95% CI 84.1,96.5) for benign tumors. Most false negatives occurred in mucinous and borderline tumors. No benign tumor was misdiagnosed as malignant by frozen section. Accuracy and negative predictive value were significantly lower in epithelial rather than germ and other cell types. Excellent agreement with regard to histologic cell type was observed (Kappa 0.81). Conclusion:, Frozen section appears to be an accurate technique for the histopathologic diagnosis of ovarian tumors. Some limitations were observed among borderline and mucinous tumors; this emphasizes the great value of frozen section in the diagnosis of ovarian tumors. [source] Characterization of the 3p12.3-pcen region associated with tumor suppression in a novel ovarian cancer cell line model genetically modified by chromosome 3 fragment transferMOLECULAR CARCINOGENESIS, Issue 12 2009Neal A.L. Cody Abstract The genetic analysis of nontumorigenic radiation hybrids generated by transfer of chromosome 3 fragments into the tumorigenic OV-90 ovarian cancer cell line identified the 3p12.3-pcen region as a candidate tumor suppressor gene (TSG) locus. In the present study, polymorphic microsatellite repeat analysis of the hybrids further defined the 3p12.3-pcen interval to a 16.1 Mb common region containing 12 known or hypothetical genes: 3ptel - ROBO2-ROBO1-GBE1-CADM2-VGLL3-CHMP2B-POU1F1-HTR1F-CGGBP1-ZNF654-C3orf38-EPHA3 -3pcen. Seven of these genes, ROBO1, GBE1, VGLL3, CHMP2B, CGGBP1, ZNF654, and C3orf38, exhibited gene expression in the hybrids, placing them as top TSG candidates for further analysis. The expression of all but one (VGLL3) of these genes was also detected in the parental OV-90 cell line. Mutations were not identified in a comparative sequence analysis of the predicted protein coding regions of these candidates in OV-90 and donor normal chromosome 3 contig. However, the nondeleterious sequence variants identified in the transcribed regions distinguished parent of origin alleles for ROBO1, VGLL3, CHMP2B, and CGGBP1 and cDNA sequencing of the hybrids revealed biallelic expression of these genes. Interestingly, underexpression of VGLL3 and ZNF654 were observed in malignant ovarian tumor samples as compared with primary cultures of normal ovarian surface epithelial cells or benign ovarian tumors, and this occurred regardless of allelic content of 3p12.3-pcen. The results taken together suggest that dysregulation of VGLL3 and/or ZNF654 expression may have affected pathways important in ovarian tumorigenesis which was offset by the transfer of chromosome 3 fragments in OV-90, a cell line hemizygous for 3p. Mol. Carcinog. © 2009 Wiley-Liss, Inc. [source] Limited prognostic value of tissue protein expression levels of BCl-2 in Danish ovarian cancer patients: from the Danish ,MALOVA' ovarian cancer studyAPMIS, Issue 8 2010ESTRID V.S. Høgdall Høgdall EVS, Christensen L, Kjaer SK, Blaakaer J, Christensen IJ, Høgdall CK. Limited prognostic value of tissue protein expression levels of BCl-2 in Danish ovarian cancer patients. APMIS 2010; 118: 557,64. The purpose of the study was to determine the expression of BCl-2 in epithelial ovarian tumors and to correlate expression levels with selected clinicopathologic parameters, time to progression and prognosis of the disease. Using tissue arrays (TA), we analyzed BCl-2 expression in tissues from 191 women diagnosed with low malignant potential ovarian tumors (LMP) and from 582 patients diagnosed with ovarian cancer (OC). Using 30% as cutoff level for BCl-2 overexpression, 5% of LMPs were positive with a higher proportion of serous ovarian tumor of LMP, compared to mucinous ovarian tumor of LMP (p = 0.02). Women with a BCl-2-positive LMP tumor were older than women with a BCl-2 negative tumor (p = 0.02). Ten percent of OCs were positive for BCl-2 expression (,30%). No significant association was found between BCl-2 expression levels and histologic type of tumors (serous vs mucinous, p = 0.19). A 30% cutoff value or a percentage scale showed that BCl-2 expression had no prognostic value, both in univariate and in multivariate survival analyses. No difference in time to progression was observed between patients with BCl-2-positive and negative tumors. These data suggest that BCl-2 expression may not be of important clinical value in the treatment of Danish OC patients. [source] Expression of the nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 is a prognostic factor in human ovarian cancerCANCER, Issue 8 2008Aurelia Noske MD Abstract BACKGROUND The human nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 (CRM1) mediates the nuclear export of proteins and messenger RNAs and, thus, is an important regulator of subcellular distribution of key molecules. Whereas cell-biologic studies have suggested a fundamental role for CRM1 in the regulation of mitosis, the expression of this protein in human tumor tissue has not been investigated to date. METHODS In this study, the expression of CRM1 was analyzed in a cohort of 88 ovarian tumors and 12 ovarian cell lines for the first time to the authors' knowledge. RESULTS Immunohistochemistry revealed increased nuclear (52.7%) and cytoplasmic (56.8%) expression of CRM1 in 74 carcinomas compared with the expression revealed in borderline tumors and benign lesions. Similarly, CRM1 expression was increased in ovarian cancer cell lines compared with human ovarian surface epithelial cells. Cytoplasmic CRM1 expression was related significantly to advanced tumor stage (P = .043), poorly differentiated carcinomas (P = .011), and higher mitotic rate (P = .008). Nuclear CRM1 was associated significantly with cyclooxygenase-2 (COX-2) expression (P = .002) and poor overall survival (P = .01). Because it was demonstrated previously that blocking of CRM1 by leptomycin B (LMB) contributes to the inhibition of nuclear export, the authors used a set of mechanistic assays to study the effects of CRM1 inhibition in cancer cells. Treatment of OVCAR-3 cells with LMB revealed a significant reduction of cell proliferation and increased apoptosis as well as suppressed interleukin-1,-induced COX-2 expression. CONCLUSIONS The current results indicated that CRM1 is expressed in a subpopulation of ovarian carcinomas with aggressive behavior and is related to poor patient outcome. A correlation also was demonstrated between CRM1 and COX-2 expression in ovarian cancer tissue. Furthermore, the treatment of ovarian cancer cells with LMB revealed a reduction in COX-2 expression. Therefore, the authors suggest that CRM1 may be an interesting biomarker for the assessment of patient prognosis and a molecular target for anticancer treatment. Cancer 2008. © 2008 American Cancer Society. [source] Wilms tumor gene protein 1 is associated with ovarian cancer metastasis and modulates cell invasionCANCER, Issue 7 2008Maria V. Barbolina PhD Abstract BACKGROUND Although metastatic disease is the primary cause of death from epithelial ovarian carcinoma, to the authors' knowledge the cellular mechanisms that regulate intraperitoneal metastasis are largely unknown. Metastasizing ovarian carcinoma cells encounter a collagen-rich microenvironment because the submesothelial matrix is comprised mainly of interstitial collagens Types I and III. METHODS Immunohistochemistry using primary and metastatic ovarian carcinoma samples was employed to detect expression of Wilms tumor gene protein 1 (WT1). Three-dimensional (3D) collagen culture, real-time reverse transcriptase-polymerase chain reaction, and immunofluorescent staining were used to evaluate changes in WT1 RNA and protein expression in response to 3D collagen culture. Boyden chamber invasion assay, scratch-wound motility assay, and Western blot analysis were used to establish the function of WT1 in ovarian carcinoma cells. RESULTS To model intraperitoneal invasion in vitro, ovarian cancer cells were cultured in a 3D collagen microenvironment. 3D collagen culture resulted in robust induction of WT1 at the mRNA and protein levels. WT1 expression was prevalent in primary ovarian tumors and was retained in paired peritoneal metastases. Functional studies supported a role for WT1 in intraperitoneal invasion, because siRNA knockdown of WT1 expression reduced the ability of ovarian cancer cells to invade 3D collagen gels. CONCLUSIONS The data from the current study identify a novel regulatory mechanism for the control of WT1 expression and provide evidence for a functional role of WT1 protein in the control of cellular invasive activity. Cancer 2008. ©2008 American Cancer Society. [source] 2C4, a monoclonal antibody against HER2, disrupts the HER kinase signaling pathway and inhibits ovarian carcinoma cell growthCANCER, Issue 12 2005Noriyuki Takai M.D. Abstract BACKGROUND Human epidermal growth factor receptor 2 (HER2) is overexpressed in 25,30% of ovarian carcinoma cases and a correlation between increased HER2 expression and decreased survival has been demonstrated. HER2 is a ligand-less member of the HER family that functions as the preferred coreceptor for epidermal growth factor receptor (EGFR), HER3, and HER4. METHODS An approach was developed to target HER2's role as a coreceptor using a monoclonal antibody, 2C4, which sterically hinders HER2's recruitment into a functional HER complex. RESULTS HER2 was robustly expressed in all eight ovarian carcinoma cell lines; expression of EGFR and HER3 was variable. Even though four of the eight cell lines responded to EGF, 2C4 antibody moderately inhibited in vitro proliferation of only two cell lines (OVCA433 and SK-OV-3). Furthermore, ligand-stimulated p-MAPK expression was inhibited by 2C4 only in these two cell lines after exposure to EGF. Immunoprecipitation and eTag analysis revealed that OVCA433 expressed heterodimers of EGFR/HER2, and these heterodimers were disrupted after treatment with 2C4, whereas OVCA432 cells did not have these heterodimers. In murine xenograft experiments, the in vivo growth of OVCA433, but not of OVCA432, ovarian carcinoma cells was significantly inhibited by 2C4 treatment of the mice. CONCLUSION 2C4 is able to disrupt the HER signaling pathway and inhibit the in vitro and in vivo growth of ovarian carcinoma cell lines. The response appears limited to lines in which HER2 heterodimers were able to transduce proliferative signals. Our findings suggest a strong rationale to conduct clinical trials of 2C4 in a subset of patients with ovarian tumors. Cancer 2005. © 2005 American Cancer Society. [source] Human ovarian carcinoma cells: Histone deacetylase inhibitors exhibit antiproliferative activity and potently induce apoptosisCANCER, Issue 12 2004Noriyuki Takai M.D., Ph.D. Abstract BACKGROUND Histone deacetylase inhibitors (HDACIs) can inhibit proliferation, stimulate apoptosis, and induce cell cycle arrest in malignant cells. METHODS The authors investigated the effects of four HDACIs on nine ovarian carcinoma cell lines in vitro and in vivo. Ovarian carcinoma cells were treated with a variety of HDACIs, and their effects on cell growth, the cell cycle, apoptosis, and related events were investigated. The ability of valproic acid (VPA) to inhibit the growth of ovarian tumors in immunodeficient mice was also assessed. RESULTS Clonogenic assays showed that all ovarian carcinoma cell lines were sensitive to the growth-inhibitory effects of the HDACIs. Cell cycle analysis indicated that their exposure to HDACIs decreased the proportion of cells in S phase and increased the proportion of cells in the G0/G1 and/or G2/M phases of the cell cycle. Terminal deoxynucleotidyltransferase-mediated uridine triphosphate end-labeling assays demonstrated that HDACIs induced apoptosis, which occurred in concert with alterations in the expression of genes related to apoptosis, cell growth, and malignant phenotype, including the activation of caspase-9 and caspase-3. Chromatin immunoprecipitation analysis revealed a notable increase in levels of acetylated histones associated with the p21 promoter after treatment with suberoylanilide bishydroxamine. In addition, in experiments involving nude mice, VPA significantly inhibited human ovarian tumor growth without toxic side effects. CONCLUSIONS The results of the current study suggest that HDACIs may be particularly effective in the treatment of ovarian tumors. Cancer 2004. © 2004 American Cancer Society. [source] | ||||||||||||||||||||||