Characteristics of physical violence against pregnant women - analysis of medico-legal data and literature review.

Pregnancy is a period which is especially sensitive to physical violence and its aftermath. Subjecting a pregnant woman to violence can have negative effects on both the mother as well as the child. In Poland, there are programs, such as the Blue Card, aimed at protection against violence, however the phenomenon is underestimated. Documentation covering forensic examinations carried out at the request of the police or privately at the Department of Forensic Medicine in Poznan in the years 2015-2020 was analyzed. Out of 7,689 cases, 22 were concluded to meet the criteria of violence against pregnant women. The cases were then further analyzed, consideration of the victim's age, professional status, relations with the perpetrator, form of physical violence, and medical assistance. The average age of the women at the time of the incident was 31.1 years. In 90.1% of the cases, the perpetrator was a known man, usually a current or former partner. The most common injuries were abrasions and bruises, while the most common locations of injuries were the head, neck, and arms. The most common forms of violence were grappling, kicking, and hitting with an open hand. Over 72% of the women sought medical attention after the incident. There is a need for educational programs concerning the effects of violence during pregnancy and ways to help. Gynecologists and midwives play an especially important role, by having direct contact with the patient, thus being able to quickly identify victims of violence and take actions to secure safe environment for the woman and the child.

Analysis of the Polymorphisms and Expression Levels of the BCL2, BAX and c-MYC Genes in Patients with Ovarian Cancer.

Ovarian cancer (OC) is one of the biggest problems in gynecological oncology and is one of the most lethal cancers in women worldwide. Most patients with OC are diagnosed at an advanced stage; therefore, there is an urgent need to find new biomarkers for this disease. Gene expression profiling is proving to be a very effective tool for exploring new molecular markers for OC patients, although the relationship between such markers and patient survival and clinical outcomes is still elusive. Moreover, polymorphisms in genes encoding both apoptosis-associated proteins and oncoproteins may serve as key markers of cancer susceptibility. The aim of our study was to analyze the polymorphisms and expressions of the BCL2, BAX and c-MYC genes in a group of 198 women, including 98 with OC. The polymorphisms and mRNA expressions of the BCL2, BAX and c-MYC genes were analyzed using real-time PCR. The analysis of the BAX (rs4645878; G>A) and c-MYC (rs4645943; C>T) polymorphisms showed no association with ovarian cancer risk. The BCL2 polymorphism (rs2279115; C>A) showed a significant difference in the frequency of genotypes between the studied groups (CC: 23.47% vs. 16.00%, AA: 25.51% vs. 37.00%; p = 0.046; OR = 1.61). Furthermore, the expression levels of the BCL2 and c-MYC genes showed a decrease at the transcript level for OC patients compared to the control group (BCL2: 17.46% ± 3.26 vs. 100% ± 8.32; p < 0.05; c-MYC: 37.56% ± 8.16 vs. 100% ± 9.12; p < 0.05). No significant changes in the mRNA level were observed for the BAX gene (104.36% ± 9.26 vs. 100% ± 9.44; p > 0.05). A similar relationship was demonstrated in the case of the protein expressions of the studied genes. These findings suggest that the CC genotype and C allele of the BCL2 polymorphism could be genetic risk factors for OC development. A gene expression analysis indicated that BCL2 and c-MYC are associated with OC risk.

Correction: Pakula et al. Deciphering the Molecular Mechanism of Spontaneous Senescence in Primary Epithelial Ovarian Cancer Cells. Cancers 2020, 12, 296.

In the original publication [...].

Pro-cancerogenic effects of spontaneous and drug-induced senescence of ovarian cancer cells in vitro and in vivo: a comparative analysis.

BACKGROUND: Clinical outcomes of cancer cell senescence are still elusive. Here, we reveal and compare pro-cancerous activity of spontaneously and drug-inducible senescent ovarian cancer cells. Experiments were performed on tumors and tumor-derived primary epithelial ovarian cancer cells (pEOCs) that were obtained from chemotherapy-naïve patients and from patients who received carboplatin (CPT) and paclitaxel (PCT) before cytoreduction. RESULTS: The analysis of tumors showed that senescent cancer cells are present in patients from both groups, albeit most frequently and covering a greater area in tissues from chemotherapy-positive women. This in vivo senescence of pEOCs translated to an expression of senescence markers in early-passage cells in vitro. A conditioned medium from senescent pEOCs fueled the cancer progression, including adhesion of non-senescent pEOCs to normal peritoneal cells, and their increased proliferation, migration, invasion, and EMT. Senescent pEOCs' secretome promoted angiogenic activity of vascular endothelium, induced senescence of normal peritoneal cells, reprogrammed their secretome towards hypersecretion of cancer-promoting proteins, and stimulated motility of cancer cells subjected to a mesothelium- and fibroblast-derived medium. The most striking finding was, however, that spontaneously senescent pEOCs supported all the above pro-cancerous effects more efficiently than drug-inducible senescent cells, which was plausibly related to augmented release of several cancer spread mediators by these cells. The prevalence of spontaneously senescent pEOCs was most evident in experiments on mice when they were able, unlike the drug-inducible cells, to promote the development of drug-sensitive i.p. xenografts. CONCLUSIONS: Our study shows that spontaneous senescence of pEOCs should be treated as an independent pathogenetic factor of cancer progression.

Using a Modified Polysaccharide as a Hemostatic Agent Results in Less Reduction of the Ovarian Reserve after Laparoscopic Surgery of Ovarian Tumors-Prospective Study.

Background and Objectives: The study investigated whether the method of achieving hemostasis affects the ovarian reserve in patients undergoing laparoscopic surgery due to ovarian tumors or cysts. Materials and Methods: Patients with unilateral tumors or ovarian cysts, who qualified for laparoscopic tumor enucleation, were randomly selected to receive modified polysaccharides or bipolar coagulation. Ovarian reserve was analyzed by anti-Mullerian hormone (AMH) level. Results: The study included 38 patients: 19 patients in the modified polysaccharide group and 19 in the bipolar coagulation group. Patients after bipolar coagulation treatment had statistically significantly lower AMH 6 months after surgery compared to the group treated with modified starch. The levels of AMH in the study and control groups were 3.96 +/- 2.12 vs. 2.51 +/- 1.39 ng/mL, respectively; p = 0.018. A statistically significant decrease in AMH was also demonstrated in the bipolar coagulation group as compared to the preoperative assessment (p = 0.049). There was no statistically significant decrease in AMH in the group of patients treated with the modified starch. Conclusions: Using a modified polysaccharide during laparoscopic cystectomy is effective and has a positive effect on the ovarian reserve compared to the use of bipolar coagulation. Both the AMH level 6 months after surgery and the percentage decrease in AMH were more favorable in the group of patients treated with modified starch.

Patient-Specific Variables Determine the Extent of Cellular Senescence Biomarkers in Ovarian Tumors In Vivo.

The mechanisms and clinical significance of the cellular senescence of tumor cells are a matter of ongoing debate. Recently, the triggers and molecular events underlying spontaneous, replicative senescence of primary epithelial ovarian cancer cells were characterized. In this study, we reanalyzed tumors obtained from ovarian cancer patients with respect to the expression of the senescence biomarkers SA-ß-Gal and γ-H2A.X and the proliferative antigen Ki67. The results showed that the tumors displayed strong heterogeneity with respect to the expression of analyzed markers. The expression of SA-ß-Gal and γ-H2A.X in the oldest patients (61-85 y.o.) was significantly higher than in the younger age groups. Conversely, the area of Ki67-positive cancer cells was greater in younger individuals. At the same time, there was a positive correlation between SA-ß-Gal expression and calendar age in FIGO III-IV and malignant ascites-positive patients. The γ-H2A.X positively correlated with age in the whole group, FIGO III-IV, and ascites-positive patients. Ki67 levels correlated negatively with the age of patients among those same groups. Collectively, our study indicated that organismal aging may determine the development of the senescence phenotype in ovarian tumors, particularly in patients with advanced disease and those accumulating malignant ascites.

Malignant Ascites Promote Adhesion of Ovarian Cancer Cells to Peritoneal Mesothelium and Fibroblasts.

Although malignant ascites (MAs) are known to contribute to various aspects of ovarian cancer progression, knowledge regarding their role in the adhesion of cancer cells to normal peritoneal cells is incomplete. Here, we compared the effect of MAs and benign ascites (BAs) on the adhesion of A2780 and OVCAR-3 cancer cells to omentum-derived peritoneal mesothelial cells (PMCs) and peritoneal fibroblasts (PFBs). The results showed that MAs stimulated the adhesion of A2780 and OVCAR-3 cells to PMCs and PFBs more efficiently than did BAs, and the strongest binding occurred when both cancer and normal cells were exposed to the fluid. Intervention studies showed that MAs-driven adhesion of A2780 cells to PMCs/PFBs depends on the presence of TGF-ß1 and HGF, whereas binding of OVCAR-3 cells was mediated by TGF-ß1, GRO-1, and IGF-1. Moreover, MAs upregulated α5ß1 integrin expression on PFBs but not on PMCs or cancer cells, vimentin expression in all cells tested, and ICAM-1 only in cancer cells. When integrin-linked kinase was neutralized in PMCs or PFBs, cancer cell adhesion to PMCs and PFBs decreased. Collectively, our report shows that MAs may contribute to the early stages of ovarian cancer metastasis by modulating the proadhesive interplay between normal and cancer cells.

Deciphering the Molecular Mechanism of Spontaneous Senescence in Primary Epithelial Ovarian Cancer Cells.

Spontaneous senescence of cancer cells remains a puzzling and poorly understood phenomenon. Here we comprehensively characterize this process in primary epithelial ovarian cancer cells (pEOCs). Analysis of tumors from ovarian cancer patients showed an abundance of senescent cells in vivo. Further, serially passaged pEOCs become senescent after a few divisions. These senescent cultures display trace proliferation, high expression of senescence biomarkers (SA--Gal, -H2A.X), growth-arrest in the G1 phase, increased level of cyclins D1, D2, decreased cyclin B1, up-regulated p16, p21, and p53 proteins, eroded telomeres, reduced activity of telomerase, predominantly non-telomeric DNA damage, activated AKT, AP-1, and ERK1/2 signaling, diminished JNK, NF-B, and STAT3 pathways, increased formation of reactive oxygen species, unchanged activity of antioxidants, increased oxidative damage to DNA and proteins, and dysfunctional mitochondria. Moreover, pEOC senescence is inducible by normal peritoneal mesothelium, fibroblasts, and malignant ascites via the paracrine activity of GRO-1, HGF, and TGF-1. Collectively, pEOCs undergo spontaneous senescence in a mosaic, telomere-dependent and telomere-independent manner, plausibly in an oxidative stress-dependent mechanism. The process may also be activated by extracellular stimuli. The biological and clinical significance of pEOC senescence remains to be explored.

Performance of Selected Models for Predicting Malignancy in Ovarian Tumors in Relation to the Degree of Diagnostic Uncertainty by Subjective Assessment With Ultrasound.

OBJECTIVES: The study's main aim was to evaluate the relationship between the performance of predictive models for differential diagnoses of ovarian tumors and levels of diagnostic confidence in subjective assessment (SA) with ultrasound. The second aim was to identify the parameters that differentiate between malignant and benign tumors among tumors initially diagnosed as uncertain by SA. METHODS: The study included 250 (55%) benign ovarian masses and 201 (45%) malignant tumors. According to ultrasound findings, the tumors were divided into 6 groups: certainly benign, probably benign, uncertain but benign, uncertain but malignant, probably malignant, and certainly malignant. The performance of the risk of malignancy index, International Ovarian Tumor Analysis assessment of different neoplasias in the adnexa model, and International Ovarian Tumor Analysis logistic regression model 2 was analyzed in subgroups as follows: SA-certain tumors (including certainly benign and certainly malignant) versus SA-probable tumors (probably benign and probably malignant) versus SA-uncertain tumors (uncertain but benign and uncertain but malignant). RESULTS: We found a progressive decrease in the performance of all models in association with the increased uncertainty in SA. The areas under the receiver operating characteristic curve for the risk of malignancy index, logistic regression model 2, and assessment of different neoplasias in the adnexa model decreased between the SA-certain and SA-uncertain groups by 20%, 28%, and 20%, respectively. The presence of solid parts and a high color score were the discriminatory features between uncertain but benign and uncertain but malignant tumors. CONCLUSIONS: Studies are needed that focus on the subgroup of ovarian tumors that are difficult to classify by SA. In cases of uncertain tumors by SA, the presence of solid components or a high color score should prompt a gynecologic oncology clinic referral.

Ovarian steroid cell tumor as an example of severe hyperandrogenism in 45-year-old woman.

Approximately, 5% of ovarian tumors have hormonal activity. Steroid cell tumors (SCTs) represent about 0.1% of all ovarian tumors. They cause hyperandrogenism associated with typical virilization. In this case report, we present 45-year-old women with unmalignant ovarian SCT-producing androgens which cause severe virilization and secondary amenorrhea lasting two years. Transvaginal ultrasound, computed tomography of adrenal glands, magnetic resonance imaging of small pelvis, laboratory tests (including serum concentration of FSH, LH, testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEA-S), as well as ROMA index) were performed. During hormonal evaluation, elevated concentrations of serum T - on admission 1.72 ng/ml and one month later 3.75 ng/ml (normal range 0.08-0.82 ng/ml) and A - 24.90 ng/ml (normal range 0.40-3.40 ng/ml) were found. The ROMA index was within the normal range. Enlargement of the left ovary by solid mass 56 × 43 mm was found during ultrasound examination. Based on small pelvis MRI scan and hormonal finding, patient was qualified for laparotomy. During this procedure, the left salpingo-oophorectomy with removal of the tumor was performed. The histopathological examination identified SCT. During follow-up examination, one day after surgery, we found serum testosterone levels within normal ranges - 0.74 ng/ml (normal range 0.08-0.82 ng/ml). This case shows that hormone-producing ovarian tumors are rare but very important clinical causes of severe hyperandrogenism.

Senescence-related deterioration of intercellular junctions in the peritoneal mesothelium promotes the transmesothelial invasion of ovarian cancer cells.

Mechanisms of transmesothelial invasion of ovarian cancer are still poorly understood. Here we examined whether this phenomenon may be determined by an expression of intercellular junctions in peritoneal mesothelial cells (PMCs). Analysis of ovarian tumors showed that cancer cells are localized below an intact layer of PMCs. The PMCs located near the invaded cancer cells displayed low expression of connexin 43, E-cadherin, occludin, and desmoglein, as well as expressed SA-ß-Gal, a marker of senescence. Experiments in vitro showed that senescent PMCs exhibited decreased levels of the four tested intercellular junctions, and that the invasion of ovarian cancer cells through the PMCs increased proportionally to the admixture of senescent cells. Intervention studies showed that the expression of connexin 43, E-cadherin, occludin, and desmoglein in senescent PMCs could be restored upon the blockade of p38 MAPK, NF-κB, AKT, JNK, HGF, and TGF-ß1. When these molecules were neutralized, the efficiency of the transmesothelial cancer cell invasion was diminished. Collectively, our findings show that the integrity of the peritoneal mesothelium, which is determined by the expression of junctional proteins, is critical for the invasion of ovarian cancer. They also indicate a mechanism by which senescent PMCs may promote the invasive potential of cancer cells.

The expression of Platelet-derived Growth factor receptors (PDGFRs) and their correlation with overall survival of patients with ovarian cancer.

OBJECTIVES: The main aim of the study was to investigate the expression of Platelet-Derived Growth Factor Receptors alpha (PDGFR-alpha) and beta (PDGFR-beta) in malignant and benign ovarian tumors. We performed an analysis of the correlation of PDGFRs expression and stage of the disease, tumor grade and histopathological type of epithelial ovarian cancer (EOC). Additionally, we evaluated patient prognosis according to PDGFR expression. MATERIAL AND METHODS: Our study group was composed of 52 samples of EOCs, 35 samples of benign ovarian tumors (BOTs), and 21 samples of unchanged ovaries (UOs). The samples were collected from patients who had been operated on in the Division of Gynecological Surgery of the Poznan University of Medical Sciences. RESULTS: PDGFR-alpha was found to be expressed more frequently in cancer cells of EOCs, when compared with tumor cells of BOTs and epithelium of UOs. On the other hand, PDGFR-alpha receptors were present less frequently in the stroma of EOCs, when compared with the stroma of BOTs and UOs. Comparing the studied groups, there were no statistically significant differences in the expression of PDGFR-beta. The expression of both PDGFRs was not related to the FIGO stage, grade or histopathological type of EOCs. The expression of the PDGFR-beta receptor in cancer cells was associated with an improved overall survival among patients with EOCs. Patient prognosis was not affected by either PDGFR-alpha expres- sion or by PDGFR-beta tumor stroma expression. CONCLUSIONS: The expression of PDGFR-alpha is significantly different when comparing EOCs, BOTs and UOs. However, the prognosis of EOC only seems to be affected by PDGFR-beta expression in cancer cells.

The Epithelial-Mesenchymal Transition Initiated by Malignant Ascites Underlies the Transmesothelial Invasion of Ovarian Cancer Cells.

The role of the epithelial-mesenchymal transition (EMT) in ovarian cancer cell progression is unquestioned. In this report, we describe that malignant ascites, fluid that accumulates in the peritoneal cavity in a large group of patients with ovarian cancer, stimulate EMT in two representative ovarian cancer cell lines (A2780, SKOV-3). In addition, we identify the ascites-derived mediators of EMT and signaling pathways initiated in the cancer cells that underlie this phenomenon. Finally, we demonstrate that EMT induced in the cancer cells in response to the malignant ascites contributes to their increased transmesothelial invasion. Altogether, our study provides new insight into the mechanistic aspects of the malignant ascites-dependent exacerbation of the intraperitoneal progression of ovarian cancer.

Mitochondria-related oxidative stress contributes to ovarian cancer-promoting activity of mesothelial cells subjected to malignant ascites.

Very little is known about the mechanisms by which malignant ascites modulates the cancer-promoting activity of human peritoneal mesothelial cells (HPMCs). Because malignant ascites induces pro-tumoral senescence in HPMCs, here we examined if this effect could be driven by oxidative stress. The study showed that malignant ascites generated by serous ovarian tumors induced oxidative damage to the DNA (γH2A.X, 53BP1, 8-hydroxy-2'-deoxyguanosine) and lipids (8-isoprostane) in HPMCs as well as increased the production of mitochondrial superoxides and cellular peroxides in these cells. This activity coincided with increased activity of two enzymes involved in the mitochondrial production of oxidants, i.e. cytochrome c oxidase and NADH dehydrogenase, decreased mitochondrial inner membrane potential, increased mitochondrial mass, and increased the activity of peroxisome proliferator-activated receptor gamma coactivator-1 alpha. Increased production of superoxides and peroxides in cells subjected to the malignant ascites was effectively reduced when the fluid was pre-incubated with neutralizing antibodies against hepatocyte growth factor. Moreover, when HPMCs subjected to the malignant ascites were protected against oxidative stress with a spin-trap scavenger of reactive oxygen species, they displayed decreased expression of senescence-associated ß-galactosidase and their potential to stimulate cancer cell adhesion, proliferation, and migration was significantly diminished. Collectively, our findings indicate that improved ovarian cancer cell progression in response to HPMCs exposed to malignant ascites may be associated with the development of profound oxidative stress in these cells.

The Proangiogenic Capabilities of Malignant Ascites Generated by Aggressive Ovarian Tumors.

Here we examined whether malignant ascites may determine ovarian tumor angiogenesis, and if so whether ascites generated by highly aggressive serous and undifferentiated cancers are more proangiogenic than those from less aggressive clear cell and endometrioid tumors. Angiogenesis was analyzed according to expression of CD31, CD34, and connexin 43. Proliferation and migration of endothelial cells were tested using fluorescence-based methods. The quantification of angiogenic agents and hypoxia-inducible factor 1α (HIF-1α) was performed using specific immunoassays. Results showed that the expression of CD31 and CD34 in serous and undifferentiated tumors was greater, whereas endothelial expression of connexin 43 was lower than in clear cell and endometrioid lesions. Serous cancers that formed in the presence of ascites displayed increased expression of connexin 43 in vascular smooth muscles as compared with tumors developed in the fluid's absence. Endothelial cells exposed to ascites from serous and undifferentiated tumors proliferated and migrated more vigorously than cells subjected to ascites from clear cell and endometrioid cancers. They also exhibited an increased level of HIF-1α and produced increased amounts of multiple proangiogenic agents. Our results indicate that high vascularization of aggressive ovarian tumors may be associated with profound angiogenic capabilities of ascites generated by these tumors.

Severe hyperandrogenemia in postmenopausal woman as a presentation of ovarian hyperthecosis. Case report and mini review of the literature.

Ovarian hyperthecosis (OH) is characterized by the presence of abundant luteinized theca cells in ovaries that secret androgen. It typically presents as severe hyperandrogenism and/or virilization in postmenopausal woman. Here we describe a 66-year old woman with presentation of severe hirsutism, alopecia, clitoromegaly and laboratory finding of significantly elevated serum total testosterone concentration and hyperinsulinemia. Performed imaging studies revealed normal sized, homogeneous ovaries, signs of endometrial hypertrophy and normal adrenal glands. Due to severe hyperandrogenemia and signs of endometrial hypertrophy, the total abdominal hysterectomy with bilateral salpingo-oophorectomy has been performed. Pathological examination revealed OH and endometrial hyperplasia. Androgenic activity of ovarian stromal cells has been confirmed using alpha-inhibin histochemical staining. Postmenopausal hyperandrogenemia is a diagnostic and therapeutic challenge and the imaging studies often may be misleading and require careful and critical consideration.

Ovarian cancer-derived ascitic fluids induce a senescence-dependent pro-cancerogenic phenotype in normal peritoneal mesothelial cells.

PURPOSE: After the seeding ovarian cancer cells into the peritoneal cavity, ascitic fluid creates a microenvironment in which these cells can survive and disseminate. The exact nature of the interactions between malignant ascitic fluids and peritoneal mesothelial cells (HPMCs) in ovarian cancer progression has so far remained elusive. Here we assessed whether malignant ascitic fluids may promote the senescence of HPMCs and, by doing so, enhance the acquisition of their pro-cancerogenic phenotype. METHODS: Primary omentum-derived HPMCs, ovarian cancer-derived cell lines (A2780, OVCAR-3, SKOV-3), malignant ascitic fluids and benign ascitic fluids from non-cancerous patients were used in this study. Ovarian cancer cell proliferation, as well as HPMC proliferation and senescence, were determined using flow cytometry and ß-galactosidase assays, respectively. Ovarian cancer cell migration was quantified using a Transwell assay. The concentrations of soluble agents in ascitic fluids, conditioned media and cell lysates were measured using DuoSet® Immunoassay Development kits. RESULTS: We found that HPMCs, when exposed to malignant ascitic fluids, exhibited decreased proliferation and increased senescence rates. The malignant ascitic fluids were found to contain elevated levels of HGF, TGF-ß1 and GRO-1, of which HGF and GRO-1 were able to induce senescence in HPMCs. We also found that HPMCs subjected to malignant ascitic fluids or exogenously added HGF and GRO-1 stimulated ovarian cancer cell progression, which was manifested by an increased production of HA (adhesion), uPA (proliferation), IL-8 and MCP-1 (migration). CONCLUSION: Our results indicate that malignant ascitic fluids may contribute to ovarian cancer progression by accelerating the senescence of HPMCs.

Biochemical composition of malignant ascites determines high aggressiveness of undifferentiated ovarian tumors.

Although undifferentiated tumors are the most lethal among all ovarian cancer histotypes, the exact reasons for this situation are unclear. This report was aimed at investigating whether the high aggressiveness of undifferentiated ovarian cancer may be associated with a biochemical composition of malignant ascites accumulating in the peritoneal cavity. We analyzed ascites from patients with undifferentiated, high-grade serous, endometrioid and clear-cell ovarian cancers, and from non-cancerous patients with respect to a group of soluble agents involved in cancer cell progression. Moreover, the effect of these fluids on proliferation and migration of ovarian cancer cells (A2780, OVCAR-3 and SKOV-3) was evaluated. The study showed that the level of all tested proteins in malignant ascites was higher than in the benign fluids. Concentration of 9/11 agents (CCL2, CXCL1, CXCL5, CXCL8, CXCL12, HGF, PAI-1, TGF-ß1 and VEGF) was the greatest in the fluids from undifferentiated cancer, while the level of remaining 2 (IL-6 and uPA) was the highest in ascites from serous carcinoma. Proliferation of cancer cells was the most effective when they were subjected to ascites from patients with undifferentiated and serous cancer, whereas the migration was the highest in the case of undifferentiated tumors. Our findings indicate that the aggressiveness of undifferentiated ovarian tumors may be associated with the composition of malignant ascites, in particular the concentration of specific proinflammatory, cancer-promoting agents.

External validation of the IOTA ADNEX model performed by two independent gynecologic centers.

OBJECTIVES: The external, two-center validation of the IOTA ADNEX model for differential diagnosis of adnexal tumors. METHODS: A total of 204 patients with adnexal masses (134 benign and 70 malignant) treated at the Division of Gynecologic Surgery, Poznan University of Medical Sciences, Poland (Center I), and 123 patients (89 benign and 34 malignant) from the Department of Obstetrics and Gynecology, Clinica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain (Center II), were enrolled into the study. RESULTS: ADNEX achieved high accuracy in discriminating between malignant and benign ovarian tumors in both centers (79.9% and 81.3% in Centers I and II, respectively). Multiclass accuracy was substantially lower than in binary classification (malignant vs. benign): 64.2% and 74.0% in Centers I and II, respectively. Sensitivity and specificity for the diagnosis of specific tumor types in Center I were as follows: benign tumors - 72.4% and 94.3%; borderline tumors - 33.3% and 87.0%, stage I ovarian cancers - 00.0% and 91.8%; stage II-IV ovarian cancers - 68.2% and 83.1%; and metastatic tumors - 00.0% and 99.5%. Sensitivity and specificity in Center II were as follows: benign tumors - 75.3% and 97.1%; borderline tumors - 50.0% and 88.2%, stage I ovarian cancers - 40.0% and 97.5%; stage II-IV ovarian cancers - 95.0% and 88.3%; and metastatic tumors - 20.0% and 98.3%. CONCLUSIONS: ADNEX is characterized by very high accuracy in differentiating between malignant and benign adnexal tumors. However, prediction of ovarian tumor types could be more accurate.

The associations between serum VEGF, bFGF and endoglin levels with microvessel density and expression of proangiogenic factors in malignant and benign ovarian tumors.

AIM OF THE STUDY: To investigate whether serum levels of VEGF, bFGF and endoglin correlate with tumor VEGF and bFGF expression or microvessel density (MVD) in ovarian cancer. PATIENTS AND METHODS: Forty five patients with epithelial ovarian cancers (EOCs) and 38 patients with benign ovarian tumors (BOTs) were included into the study. Serum levels of VEGF, bFGF and endoglin were assessed using ELISA. The expression of VEGF and bFGF in tumor samples were evaluated using ELISA of supernatants obtained from tumor homogenization. MVD was analyzed using immunohistochemistry with antibodies against CD31, CD34 and CD105. RESULTS: Serum VEGF levels were significantly higher in EOCs than in BOTs (436.6pg/ml [19.67-2860] vs 295.5pg/ml [123-539], P=0.025). Serum endoglin levels were lowered in the group EOCs when compared to BOTs (33,720g/ml [12,220-73,940] vs 42,390pg/ml [19,380-56,910], P=0.015). There were no differences in bFGF levels between studied groups. EOCs have significantly higher CD105 MVD (25 vessels/mm2 [0-57] vs 6 vessels/mm2 [0-70], P<0.001) and tumor VEGF (405.9pg/mg protein [0-3000] vs 2.225 [0-634.7], P<0.001) expression than BOTs, while, bFGF expression was higher in BOTs than in EOCs (2076pg/mg protein [668.1-8718] vs 847.3pg/mg protein [188.9-8333], P=0.003). In patients with EOCs we have observed negative correlation between serum VEGF concentration and its tissue expression (r Spearman=-0.571, P=0.0261), and serum VEGF concentration correlated positively with CD34-MVD (r Spearman=0.545, P=0.0289). In a multiple regression analysis we have observed only the negative correlation between serum VEGF and CD105-MVD (r=-0.5288, P=0.0427). CONCLUSIONS: Serum VEGF is a useful marker for prediction of ovarian cancer MVD and tumor VEGF expression.