Assessment of the clinicopathological relevance of mesothelin level in plasma, peritoneal fluid, and tumor tissue of epithelial ovarian cancer patients.

Ovarian cancer remains the most lethal gynecologic malignancy. This is due to lack of effective screening, diagnosis predominance in late stage of disease, a high recurrence rate after primary therapy, and poor treatment response in platinum-resistant tumor. Thus, unique biomarkers, predictive of individual disease course, and prognosis are urgently needed. The aim of our study was to assess the clinicopathological significance of plasma, peritoneal fluid, and tumor tissue levels of mesothelin in epithelial ovarian cancer patients. Plasma and peritoneal fluid levels of mesothelin were measured by enzyme-linked immunosorbent assay. Tissue expression of MSLN was evaluated using quantitative real-time polymerase chain reaction. Preoperative plasma mesothelin levels were significantly higher in epithelial ovarian cancer patients in comparison to the patients with benign tumor and controls. There have been noticed significant differences in the plasma mesothelin levels based on International Federation of Gynecology and Obstetrics stage, grade, and histology type. No significant changes were observed between Kurman and Shih type I versus type II epithelial ovarian cancer. Interestingly, peritoneal fluid mesothelin levels revealed significant differences based on both grade and Kurman and Shih-type epithelial ovarian cancer. There were no relevant changes in the mesothelin level in peritoneal fluid between different stages and histology types compared to benign tumor. MSLN expression level in tumor tissue was significantly higher based on stage, grade, and Kurman and Shih-type epithelial ovarian cancer than in the benign masses. In addition, data showed significant higher MSLN expression in endometrioid tumors compared to benign masses and serous tumors. Plasma, peritoneal fluid, and tumor tissue levels of mesothelin positively correlated with level of CA125. Low mesothelin concentrations in plasma were also associated with prolonged patient survival. More importantly, we revealed that plasma mesothelin level was correlated with both peritoneal fluid mesothelin level and tumor MSLN expression. This study highlights that plasma mesothelin level may be a useful noninvasive biomarker surrogate for local tumor mesothelin status in monitoring of epithelial ovarian cancer patients.

[Why ovarian cancer cells escape from immune surveillance?]

Ovarian cancer is a malignancy of high mortality rates. In respect of the number of deaths caused by cancers it occupies the fourth place among women in Poland. Recent studies are focusing on the role of immune system in ovarian cancer pathogenesis. It has been reported that immune response against ovarian cancer cells may be inhibited by a number of immunosuppressive mechanisms active in cancer microenvironment. It causes difficulties in recognizing and destroying cancer cells by immune system which leads to the development of immune tolerance and is associated with a low efficacy of standard therapeutic strategies. In the presented paper we have described selected, new immunosuppressive mechanisms in ovarian cancer patients. They may be a novel, additional and relevant criterion that should be considered whilst developing new therapeutic strategies. Possibly, modulation of immunosuppressive mechanisms could contribute to modifying standard therapies and in consequence improve treatment outcome in ovarian cancer patients.

[The prognostic value of selected immunological factors in ovarian cancer patients]. / Prognostyczna wartosc wybranych czynników immunologicznych u chorych na raka jajnika.

Ovarian cancer is the most aggressive gynecological cancer and is often diagnosed in advanced stage. Constantly we are looking for new prognostic factors which would enable early diagnosis, increase the effectiveness of therapeutic intervention. There is to little data about immunological predictors in ovarian cancer. The tumor's microenvironment is designated by regulatory T cells, cytotoxic T cells, dendritic cells (DCs), tumor - associated macrophages (TAMs), monocytes, plasma cells and cytokines, such as IL-6, IL-8, IL-10, IL-17 and TGF-beta. Some of them are responsible for the inhibition and others induce tumor growth. Ovarian cancer patients with high ratio of CD8 + TILs to Treg present longer overall survival time (OS). The presence of T helper cells in ascites is associated with longer OS. Furthermore, patients with a lower rate plasmocytoid DCs infiltrating tumor tissue demonstrate longer progression-free survival time (PFS). Women with increased M1/M2 ratio present higher five-year survival rate. The presence of immunologically competent cells and secreted cytokines give motivation to evaluate their prognostic value. Perhaps this strategy will contribute to longer progression-free survival time and overall survival time in those patients.

Applications of T1 and T2 relaxation time calculation in tissue differentiation and cancer diagnostics-a systematic literature review.

Introduction: The purpose of this review was to summarize current applications of non-contrast-enhanced quantitative magnetic resonance imaging (qMRI) in tissue differentiation, considering healthy tissues as well as comparisons of malignant and benign samples. The analysis concentrates mainly on the epithelium and epithelial breast tissue, especially breast cancer. Methods: A systematic review has been performed based on current recommendations by publishers and foundations. An exhaustive overview of currently used techniques and their potential in medical sciences was obtained by creating a search strategy and explicit inclusion and exclusion criteria. Results and Discussion: PubMed and Elsevier (Scopus & Science Direct) search was narrowed down to studies reporting T1 or T2 values of human tissues, resulting in 404 initial candidates, out of which roughly 20% were found relevant and fitting the review criteria. The nervous system, especially the brain, and connective tissue such as cartilage were the most frequently analyzed, while the breast remained one of the most uncommon subjects of studies. There was little agreement between published T1 or T2 values, and methodologies and experimental setups differed strongly. Few contemporary (after 2000) resources have been identified that were dedicated to studying the relaxation times of tissues and their diagnostic applications. Most publications concentrate on recommended diagnostic standards, for example, breast acquisition of T1- or T2-weighted images using gadolinium-based contrast agents. Not enough data is available yet to decide how repeatable or reliable analysis of relaxation times is in diagnostics, so it remains mainly a research topic. So far, qMRI might be recommended as a diagnostic help providing general insight into the nature of lesions (benign vs. malignant). However, additional means are generally necessary to differentiate between specific lesion types.

Tumor-Associated Macrophages and Myeloid-Derived Suppressor Cells as Immunosuppressive Mechanism in Ovarian Cancer Patients: Progress and Challenges.

Cancers are complex masses of malignant cells and nonmalignant cells that create the tumor microenvironment (TME). Non-transformed cells of the TME such as tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) have been observed in the TME of ovarian cancer (OC) patients. Although these subsets may contribute to each step of carcinogenesis and are commonly associated with poor prognosis, still little is known about creation of the protumor microenvironment in OC. In this review, we focused on the nature and prognostic significance of TAMs and MDSCs in OC patients. Moreover, we discuss the main problems and challenges that must be overcome by researchers and clinicians to enrich our knowledge about the immunosuppressive microenvironment of cancers.