No abstract

Aim: 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. Methods: The study included 114 consecutive women with ovarian tumors (82 benign and 32 malignant) who were referred to our division. Results: A cut-off level of 28.0 ng/mL for OPN showed a sensitivity of 71.87% and a specificity of 89.02%. The area under the receiver-operator curve (ROC) was 0.812. There were no differences in diagnostic utility between OPN and the other studied tests. OPN levels were lower in patients with endometriotic ovarian cysts than in those with other benign ovarian tumors (14.00 vs 19.50 ng/mL; P = 0.018). The difference between the median OPN level in patients with endometriotic cysts (14.0 ng/mL) and those with malignant tumors (40.85 ng/mL) was also statistically significant (P < 0.0001). The calculated OPN/CA-125 ratio was significantly different between patients with endometriotic cysts (median, 0.36; range, 0.05-2.89) and those with other benign tumors (median, 1.25; range, 0.05-5.70) (P = 0.0002). There was also a statistically significant difference in the median OPN/CA-125 ratio between patients with endometrial cysts (median, 0.36; range, 0.05-2.89) and those with malignant tumors (median, 0.12; range, 0.01-3.39) (P = 0.004). Conclusion:The diagnostic utility of OPN is similar to that of ultrasonographic evaluation and CA-125 level assessment. Thus, OPN may be useful in differential diagnosis for less experienced ultrasonographers and is especially valuable for differential diagnosis of endometriotic cysts.

Our results indicate that malignant ascitic fluids may contribute to ovarian cancer progression by accelerating the senescence of HPMCs.

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-β-Gal, γ-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-κB, 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-β1. 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.

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.