Rafał Moszyński

Role of osteopontin in differential diagnosis of ovarian tumors

The aim of this study was to evaluate the role of the serum osteopontin (OPN) level as a biomarker for discriminating between malignant and benign ovarian tumors. Furthermore, comparisons with the diagnostic usefulness of the other tests were performed.

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

PurposeAfter 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.MethodsPrimary 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 β-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.ResultsWe 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-β1 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).ConclusionOur results indicate that malignant ascitic fluids may contribute to ovarian cancer progression by accelerating the senescence of HPMCs.

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.

An Intelligent System for Computer-Aided Ovarian Tumor Diagnosis

This article describes the fundamentals of an intelligent decision support system for the diagnosis of ovarian tumors. The system is designed to support diagnosis by less experienced gynecologists, and to gather data for continuous improvement of the quality of diagnosis. The theoretical basis for the construction of the system is the IF-sets framework, used to aggregate multiple decision-making methods, and simultaneously providing information about positive and negative diagnosis of a given tumor type.

Extracellular matrix metalloproteinase inducer (EMMPRIN) expression correlates positively with active angiogenesis and negatively with basic fibroblast growth factor expression in epithelial ovarian cancer

PurposeThe primary aim of this paper was to evaluate the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and its relationship with proangiogenic factors and microvessel density (MVD) in ovarian cancer.MethodsThe study group included 58 epithelial ovarian cancers (EOCs), 35 benign ovarian tumors, and 21 normal ovaries. The expression of EMMPRIN, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) was assessed by ELISA of tissue homogenates. Antibodies against CD105, CD31, and CD34 were used to immunohistochemically assess MVD.ResultsWe have found significantly higher EMMPRIN expression in EOC than in benign ovarian tumors and normal ovaries. Similarly, the VEGF expression was higher in EOC than in benign ovarian tumors and normal ovaries. By contrast, bFGF expression was lower in EOC than in benign ovarian tumors and ovary samples. EMMPRIN expression in EOC was directly correlated with VEGF expression and CD105-MVD, but inversely correlated with bFGF expression. Grade 2/3 ovarian cancers had increased expression of EMMPRIN and VEGF, increased CD105-MVD, and lowered expression of bFGF compared to grade 1 ovarian cancers. Moreover, EMMPRIN expression was higher in advanced (FIGO III and IV) ovarian cancer.ConclusionsThe upregulation of EMMPRIN and VEGF expression is correlated with increased CD105-MVD and silenced bFGF, which suggests early and/or reactivated angiogenesis in ovarian cancer. Aggressive EOC is characterized by the following: high expression of EMMPRIN and VEGF, high CD105-MVD, and low expression of bFGF.

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-β1 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.

Serum arylesterase and paraoxonase activities in patients with ovarian tumors

OBJECTIVE High levels of toxic reactive oxygen species have been found in many types of cancer cells. Serum arylesterase (ARE) and paraoxonase (PON) are esterase enzymes that have strong antioxidant characteristics. The main purpose of our study was to evaluate the activity of ARE and PON in the sera of patients with ovarian cancer and benign ovarian tumors. MATERIALS AND METHODS This study included 30 patients with ovarian cancer, 42 patients with benign ovarian tumors, and 19 healthy age- and sex-matched individuals. ARE and PON activities were measured using spectrophotometry. RESULTS Serum ARE activity was significantly different among the three studied groups (p<0.0001). However, posthoc tests revealed that ARE activity was lower in the benign ovarian tumor group (median, 1.53 U/mL; range, 0.43-2.47 U/mL) than in the other groups. There were no differences in ARE activity between patients with ovarian cancer (1.89 U/mL; range, 1.01-2.56 U/mL) and healthy individuals (2.05 U/mL; range, 0.79-2.44 U/mL). We found no differences in PON activity or the PON:ARE activity ratio between the studied groups. Tumor size in the benign ovarian tumor group was positively correlated with ARE activity (R Spearman=0.46, p=0.003) and negatively correlated with PON activity (R Spearman=-0.50, p=0.001). The ARE and PON activities were not influenced by histological type, ovarian cancer grade, or disease advancement. CONCLUSION ARE activity is higher in patients with ovarian cancer than in patients with benign ovarian tumors; however, the serum activity of ARE is similar between patients with cancer and healthy individuals.

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.

Recurrent endometrial hyperplasia as a presentation of estrogen-secreting thecoma – case report and minireview of the literature

Abstract Thecoma is a rare ovarian tumor, presenting usually in postmenopausal women as unilateral, benign, solid lesion. About 15% of affected patients develop endometrial hyperplasia (EH) and 20% are diagnosed with endometrial cancer. In this case report, we present 60-year-old women admitted because of recurrent spotting of 5 years duration, which started 1 year after menopause. In history, the patient underwent three times curettage procedures and once (1 year before admission) had estradiol levels typical for reproductive-age women. At admission, we found elevated serum levels of estradiol (222.5 pg/ml) and a small mass in the right ovary. The markers of germ cell tumors were negative. After the initial diagnosis, the patient was qualified for total abdominal hysterectomy with bilateral salpingo-oophorectomy. The histopathological examination and immunohistochemical staining confirmed the thecoma diagnosis. In follow-up examination after 8 weeks, we found decreased serum estradiol levels and relief of the symptoms. In conclusion, we want to underline that in cases of EH, especially in patients with a history of recurrences, the special attention should be paid for differential diagnosis. In such cases, the estrogen-secreting tumors should be excluded.

Malignant presentation of uterine lymphangioleiomyomatosis

OBJECTIVE The main aim of this case report was to present the method of diagnosis, management, and the 12-year-follow-up of a patient diagnosed with primary uterine lymphangioleiomyomatosis (LAM). CASE REPORT A 47-year-old woman was admitted to the Department of Thoracosurgery due to pulmonary lesions suspected to be metastatic. The potential primary site of the neoplasm was not identified by previous imaging studies and specialist counseling. The patient had a history of total abdominal hysterectomy without ovaries due to a uterine tumor recognized as cellular leiomyoma and left salpingo-oophorectomy due to a solid ovarian tumor also recognized as leiomyoma. She had previously undergone the removal of a left kidney angiomyolipoma. After histopathological examination of the pulmonary lesions and repeated evaluation of the ovarian and uterine tumors, the diagnosis of primary uterine LAM with metastases to the ovary and the lungs was established. Although new metastatic lesions occurred, the patient remained in good condition during the 12-year-follow-up. CONCLUSION The history of our patient and review of the literature suggest that although uterine LAM presents malignant features (i.e., metastasis), the disease is long lasting and the patient can be in good condition for a number of years.