Background The oncogenesis of ovarian cancer is poorly understood. The aim of this study was to identify mRNAs differentially expressed between moderately and poorly differentiated (MD/PD) serous ovarian carcinomas (SC), serous ovarian borderline tumours (SBOT) and superficial scrapings from normal ovaries (SNO), and to correlate these mRNAs with clinical parameters including survival. Methods Differences in mRNA expression between MD/PD SC, SBOT and SNO were analyzed by global gene expression profiling (n = 23), validated by RT-qPCR (n = 41) and correlated with clinical parameters. Results Thirty mRNAs differentially expressed between MD/PD SC, SBOT and SNO were selected from the global gene expression analyses, and 21 were verified (p<0.01) by RT-qPCR. Of these, 13 mRNAs were differentially expressed in MD/PD SC compared with SNO (p<0.01) and were correlated with clinical parameters. ZNF385B was downregulated (FC = −130.5, p = 1.2×10−7) and correlated with overall survival (p = 0.03). VEGFA was upregulated (FC = 6.1, p = 6.0×10−6) and correlated with progression-free survival (p = 0.037). Increased levels of TPX2 and FOXM1 mRNAs (FC = 28.5, p = 2.7×10−10 and FC = 46.2, p = 5.6×10−4, respectively) correlated with normalization of CA125 (p = 0.03 and p = 0.044, respectively). Furthermore, we present a molecular pathway for MD/PD SC, including VEGFA, FOXM1, TPX2, BIRC5 and TOP2A, all significantly upregulated and directly interacting with TP53. Conclusions We have identified 21 mRNAs differentially expressed (p<0.01) between MD/PD SC, SBOT and SNO. Thirteen were differentially expressed in MD/PD SC, including ZNF385B and VEGFA correlating with survival, and FOXM1 and TPX2 with normalization of CA125. We also present a molecular pathway for MD/PD SC.

The AKT signaling pathway is crucial for cancer cell survival. The objective of this study was to analyze the expression and clinical role of this pathway in serous ovarian carcinoma. Phospho-AKT and phospho-mammalian target of rapamycin protein expression was studied in 269 ovarian carcinomas (159 effusions, 38 primary carcinomas, 72 solid metastases) using immunohistochemistry. The association between AKT, mammalian target of rapamycin, and DJ-1 in effusions was quantitatively analyzed using flow cytometry. AKT phosphorylation status in effusions was further studied using Western blotting. Phospho-AKT and phospho-mammalian target of rapamycin were detected in the majority of tumors at all anatomical sites. Phospho-AKT expression in effusions was higher in grade 3 versus grades 1 and 2 tumors (P = .013). Flow cytometry analysis showed association between AKT, mammalian target of rapamycin, and DJ-1 expression (P < .001). Higher phospho-AKT Thr308/pan-AKT ratio by Western blotting was associated with more advanced International Federation of Gynecology and Obstetrics stage (P = .018) and a trend for poor response to chemotherapy at first disease recurrence (P = .051). Higher phospho-mammalian target of rapamycin protein expression in effusions by immunohistochemistry was associated with poor progression-free survival for patients with postchemotherapy effusions (P = .005). Phospho-mammalian target of rapamycin was an independent predictor of poor progression-free survival for patients with postchemotherapy effusions (P = .03). The association between activated AKT and mammalian target of rapamycin expression and clinicopathologic parameters of aggressive disease, including shorter patient survival, provides further evidence regarding the central role of this signaling pathway in ovarian carcinoma.

OBJECTIVE:Recent studies indicate that circulating calprotectin may serve as a biomarker in some cancers. We investigated whether this is the case for ovarian neoplasms. STUDY DESIGN:Calprotectin was analyzed with an enzyme-linked immunosorbent assay in EDTA-plasma collected prior to surgery from women with ovarian carcinomas (n = 89), borderline ovarian tumors (BOT, n = 39), and benign ovarian tumors (n = 71). Serum CA 125 was analyzed in the same study population. RESULTS:Median plasma calprotectin concentration was elevated in ovarian carcinoma, compared with controls, as well as compared with BOT (both P < .001). A positive correlation was found between CA 125 and calprotectin concentrations in ovarian carcinoma. Receiver operating characteristic curves demonstrated a larger area under the curve for CA 125 (0.85) as compared with calprotectin (0.70). CONCLUSION:Plasma calprotectin is elevated in invasive ovarian cancer, but when used as a tumor marker, it is inferior to CA 125.

Background. Laparoscopic management of borderline ovarian tumors is controversial. Objective. To retrospectively compare outcome after surgery by laparoscopy or laparotomy for borderline tumors. Methods. Ovarian tumors from all women operated at Ulleval University Hospital during a five-year period were re-evaluated histologically. Patients with borderline FIGO (International Federation of Gynaecology and Obstetrics) stage I tumors were retrospectively compared regarding surgery outcome following laparoscopy or laparotomy. Results. Histological re-evaluation revealed only 3 misclassifications in 608 patients. Borderline tumors represented 36% of epithelial ovarian malignancies. The 107 borderline stage I included 52 serous, 53 mucinous, and 2 endometrioid tumors. Thirty-eight patients were operated on primarily by laparoscopy and 69 by laparotomy (including 14 women starting with laparoscopy). In the laparoscopy group, more women were premenopausal (63% versus 35%, p = 0.01) and median tumor diameter was smaller (8.6 versus 16.4 cm, p < 0.001) as compared to the laparotomy group. When tumor diameter exceeded 10 cm, intraoperative tumor rupture was significantly more frequent during laparoscopy than during laparotomy (p = 0.01). Less postoperative complications were seen after laparoscopic operations (p = 0.034), but laparoscopic surgeries were less extensive, without hysterectomy, as compared to laparotomy. During the 14-78 months follow-up time, no relapse occurred in either group. After fertility-sparing surgery, there was no statistical significant difference regarding successful pregnancies between the two groups. Conclusions. Laparoscopic treatment of borderline ovarian tumors is feasible if tumor is of moderate size (diameter below 10 cm), gives fewer complications, and shorter hospital stay. Long-term follow-up of larger materials is needed to determine the ultimate recurrence risk as well as fertility rates.

The objective of this study was to compare the expression of the nerve growth factor (NGF) receptors TrkA and p75 in ovarian borderline tumors, International Federation of Gynecology and Obstetrics (FIGO) stage I carcinomas and advanced-stage (FIGO stage III-IV) carcinomas, and to assess a possible association between NGF receptor expression and mitogen-activated protein kinase (MAPK) activation in borderline tumors and FIGO stage I carcinomas. Sections from 119 borderline tumors, 57 FIGO stage I invasive ovarian carcinomas, and 56 advanced-stage carcinomas were evaluated for expression of activated phospho-TrkA (p-TrkA) and p75 using immunohistochemistry. MAPK activation was analyzed in stage I carcinomas and borderline tumors using phospho-specific antibodies against the extracellular-regulated kinase (p-ERK), the high osmolarity glycerol response kinase (p-p38), and the c-jun amino-terminal kinase (p-JNK). p-TrkA membrane expression was significantly more frequent in advanced-stage carcinomas compared with both borderline and stage I carcinomas (P < .001). p75 membrane expression was comparable in the 3 groups (P > .05). p-ERK and p-p38 expression was comparable in borderline and stage I carcinomas, whereas p-JNK was more frequently expressed in stage I ovarian carcinomas (P < .001). NGF receptor expression showed no association with MAPK activation in borderline and stage I carcinomas. In conclusion, expression of biologically active p-TrkA receptor at the cell membrane is up-regulated along tumor progression in ovarian carcinoma, whereas p75 expression remains unaltered. These data provide further evidence regarding the clinical role of p-TrkA in ovarian carcinoma. NGF receptors probably signal via MAPK-independent pathways in ovarian carcinoma.

Background . Laparoscopic management of borderline ovarian tumors is controversial. Objective. To retrospectively compare outcome after surgery by laparoscopy or laparotomy for borderline tumors. Methods. Ovarian tumors from all women operated at Ullevål University Hospital during a five-year period were re-evaluated histologically. Patients with borderline FIGO (International Federation of Gynaecology and Obstetrics) stage I tumors were retrospectively compared regarding surgery outcome following laparoscopy or laparotomy. Results . Histological re-evaluation revealed only 3 misclassifications in 608 patients. Borderline tumors represented 36% of epithelial ovarian malignancies. The 107 borderline stage I included 52 serous, 53 mucinous, and 2 endometrioid tumors. Thirty-eight patients were operated on primarily by laparoscopy and 69 by laparotomy (including 14 women starting with laparoscopy). In the laparoscopy group, more women were premenopausal (63% versus 35%, p = 0.01) and median tumor diameter was smaller (8.6 versus 16.4 cm, p <0.001) as compared to the laparotomy group. When tumor diameter exceeded 10 cm, intraoperative tumor rupture was significantly more frequent during laparoscopy than during laparotomy ( p = 0.01). Less postoperative complications were seen after laparoscopic operations ( p = 0.034), but laparoscopic surgeries were less extensive, without hysterectomy, as compared to laparotomy. During the 14–78 months follow-up time, no relapse occurred in either group. After fertility-sparing surgery, there was no statistical significant difference regarding successful pregnancies between the two groups. Conclusions. Laparoscopic treatment of borderline ovarian tumors is feasible if tumor is of moderate size (diameter below 10 cm), gives fewer complications, and shorter hospital stay. Long-term follow-up of larger materials is needed to determine the ultimate recurrence risk as well as fertility rates.

Objective. To analyze the expression of the AP-2-gamma transcription factor in ovarian borderline tumors, early-stage ovarian carcinoma and advanced-stage ovarian carcinoma, and to evaluate its prognostic role in advanced-stage tumors.Methods. Sections from 14 normal ovaries, 75 borderline tumors, 22 FIGO stage I invasive ovarian carcinomas, and 306 advanced-stage (FIGO stages II-IV) ovarian carcinomas (42 primary tumors, 62 solid metastases, 202 effusions) were evaluated for expression of the transcription factor AP-2 gamma using immunohistochemistry. Sixty-three effusions and two cell lines (SKOV-3 and OVCAR-3) were additionally studied using immunoblotting. The prognostic role of AP-2 gamma in advanced-stage carcinomas was analyzed.Results. AP-2 gamma was detected in the nucleus of tumor cells in 28/75 (37%) borderline tumors, 13/22 (59%) FIGO stage I carcinomas, and 255/306 (83%) advanced-stage carcinomas (P < 0.001, Chi-square test). Benign ovaries were uniformly negative. Expression was largely limited to carcinoma cells in effusions. Solid lesions and effusions from advanced-stage carcinomas showed comparable expression. Immunoblotting showed AP-2 gamma expression in 59/61 effusions and both cell lines. AP-2 gamma expression did not correlate with survival.Conclusions. AP-2 gamma expression is upregulated in advanced-stage ovarian carcinoma compared to early-stage carcinomas, borderline tumors, and the ovarian surface epithelium, and AP-2 gamma is specifically localized to cancer cells in effusions, suggesting a role in tumor progression. The lack of predictive value for this transcription factor in advanced-stage disease may be related to its frequent expression. (C) 2005 Elsevier Inc. All rights reserved.

Objectives: The aim of this study was to investigate whether it is necessary to consider time of day and bladder filling when assessing genital prolapse. Women with prolapse often experience larger bulge and heaviness in the evening and are more bothered when the bladder is full, but it is unclear whether this has any impact on the evaluation of the prolapse. Traction on the cervix with a tenaculum is still used by some gynecologists in the examination of a prolapse. This may be painful for the patients and it is uncertain whether it yields more information than performing a maximal Valsalva maneuver. Methods: Fifteen patients scheduled for prolapse surgery were examined before 10 am and after 8 pm according to the Pelvic Organ Prolapse Quantification (POP-Q) system. In addition, traction on the cervix was compared with maximal Valsalva maneuver when assessing the cervical descent. For a clinical difference of 1 cm in prolapse size and a type I error of 5% and a power of 90%, a paired sample of 15 were necessary. Results: No clinically relevant differences could be demonstrated, neither between morning and evening examination nor between examination with a full and empty bladder. There was very good correlation in the cervical descent between maximal Valsalva maneuvers and tenaculum traction on the cervix (correlation coefficient = 0.96, P = 0.001). Conclusions: Traction on the cervix is not necessary if the patient is able to perform the Valsalva maneuver. It is unnecessary to take into account bladder filling and time of day when assessing a genital prolapse.

BACKGROUNDPostpartum haemorrhage is a major contributor to maternal morbidity and mortality.MATERIAL AND METHODSIn this case report we present a patient with intractable postpartum haemorrhage, successfully treated with selective arterial embolisation of the uterine arteries.RESULTS AND INTERPRETATIONIn most cases, primary postpartum haemorrhage can be managed with conservative treatment involving uterine massage, uterotonic drugs and uterine/vaginal packing. With persistent bleeding, vascular ligation or hysterectomy may be needed. Surgical treatment may be technically difficult and may fail to control haemorrhage. For these reasons, selective arterial embolisation of the uterine arteries represents an interesting alternative that allows preservation of future fertility.