scholarly journals Absence of PD-L1 on tumor cells is associated with reduced MHC I expression and PD-L1 expression increases in recurrent serous ovarian cancer

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Stefanie Aust ◽  
Sophie Felix ◽  
Katharina Auer ◽  
Anna Bachmayr-Heyda ◽  
Lukas Kenner ◽  
...  
2017 ◽  
Vol 16 (4) ◽  
pp. 29-33 ◽  
Author(s):  
T. A. Bogush ◽  
A. A. Arefieva ◽  
S. A. Kaliuzhny ◽  
E. A. Bogush ◽  
S. A. Tjulandin ◽  
...  

Background. Epithelial-mesenchymal transition (EMT) is a factor related to metastatic potential of tumor cells. The most distinguishing feature of this transformation is expression of protein vimentin, which is not common for epithelial cells. Data of EMT level and clinical significance of the marker is ambiguous in prognosis of tumor different localization including ovarian cancer. Objective is characterization of EMT in ovarian cancer tissue based on quantitative analysis of co-expression level of epithelial cytokeratins and mesenchymal cells marker vimentin. Materials and methods. A quantitative assessment of co-expression level of cytokeratins and vimentin was performed by double immunofluorescence staining method (58 surgery specimens of ovarian cancer stage III), associated with flow cytometry. Results. Double immunofluorescence staining method, developed and used in the current study, was used for quantitative assessment of EMT level based on value of cytokeratin and vimentin co-expression in epithelial cells. Epithelial cells co-expressed these markers, were detected in 100 % tumor investigated with individual value differences from 10 to 86 %. Average co-expression level of cytokeratins and vimentin in subgroups with high and low level value related to median 42 % significantly varied and were 28,5 ± 7,5 and 56,3 ± 11,8 % (p = 0,02) respectively. Conclusions Serous ovarian cancer is molecular heterogeneous group with principal differences in level of EMT tumor phenotype between various patients. In half of the cases the disease is characterized by high metastatic potential of tumor cells. Co-expression of cyto-keratins and vimentin in all the tumors investigated is evidenced clinical significance of this molecular characteristic in ovarian cancer pathogenesis.


Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 698 ◽  
Author(s):  
Christine Bekos ◽  
Besnik Muqaku ◽  
Sabine Dekan ◽  
Reinhard Horvat ◽  
Stephan Polterauer ◽  
...  

In high grade serous ovarian cancer patients with peritoneal involvement and unfavorable outcome would benefit from targeted therapies. The aim of this study was to find a druggable target against peritoneal metastasis. We constructed a planar—scale free small world—co-association gene expression network and searched for clusters with hub-genes associated to peritoneal spread. Protein expression and impact was validated via immunohistochemistry and correlations of deregulated pathways with comprehensive omics data were used for biological interpretation. A cluster up-regulated in miliary tumors with NECTIN4 as hub-gene was identified and impact on survival validated. High Nectin 4 protein expression was associated with unfavorable survival and (i) reduced expression of HLA genes (mainly MHC I); (ii) with reduced expression of genes from chromosome 22q11/12; (iii) higher BCAM in ascites and in a high-scoring expression cluster; (iv) higher Kallikrein gene and protein expressions; and (v) substantial immunologic differences; locally and systemically; e.g., reduced CD14 positive cells and reduction of different natural killer cell populations. Each three cell lines with high (miliary) or low NECTIN4 expression (non-miliary) were identified. An anti-Nectin 4 antibody with a linked antineoplastic drug–already under clinical investigation–could be a candidate for a targeted therapy in patients with extensive peritoneal involvement.


2019 ◽  
Vol 69 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Liju Zong ◽  
Yuncan Zhou ◽  
Ming Zhang ◽  
Jie Chen ◽  
Yang Xiang

AbstractBlockading programmed death ligand 1 (PD-L1) shows promising results in patients with some cancers, but not in those with ovarian cancer. V-domain Ig suppressor of T cell activation (VISTA) is a recently discovered immune checkpoint protein that suppresses T cell activation. This study aimed to investigate the expression and clinical significance of VISTA in ovarian cancer as well as its relationship with PD-L1. VISTA and PD-L1 levels in 146 ovarian cancer samples were assessed using immunohistochemistry. We investigated the association between VISTA and other clinicopathological variables, including survival. The associations between the VISTA-encoding C10orf54 gene, other immune checkpoints, and survival were analyzed. VISTA was detected in 51.4% of all samples and 46.6% of PD-L1-negative samples; it was expressed in 28.8%, 35.6%, and 4.1% of tumor cells (TCs), immune cells (ICs), and endothelial cells, respectively. Furthermore, VISTA expression was associated with pathologic type and PD-L1 expression. Moreover, VISTA expression in TCs, but not in ICs, was associated with prolonged progression-free and overall survival in patients with high-grade serous ovarian cancer. The expression of C10orf54 mRNA was associated with prolonged overall survival and immune escape-modulating genes. These results showed that VISTA expression in ovarian tumor cells was associated with a favorable prognosis in patients with high-grade serous ovarian cancer; however, additional studies are required to better understand the expression and role of VISTA in ovarian cancer.


2019 ◽  
pp. 92-95
Author(s):  
D.G. Sumtsov ◽  
◽  
M.L. Kusyomenska ◽  
G.A. Sumtsov ◽  
◽  
...  

In the literature review the authors present an analysis of the current stateproblem of ovarian cancer and ways of its possible solution. According to clinicalobservations and conducted in recent decades by morphological,immunohistochemical and molecular genetic studies it is fairly proved that theprimary cause of serous ovarian cancer is the pathology of the mucous layer offallopian tube. In the fallopian tube as a result of ciculation of inflammation andcarcinogens elements arises dysplasia of the mucosa with the development of thepreinvasive and initial invasive carcinoma with subsequent damage of the ovariesand pelvic peritoneum. Retrospective studies of a significant number of women’shealth status who had a deligation or removal of fallopian tubes in previous years showed a decrease in the disease incidence of serous ovarian cancer from 30 to 90%. The conclusions about the possibility of preventive measures of ovariancancer by opportunistic salpingectomy at post-productive age are made. In many world countries (Canada, China, France, Italy, Austria) the introduction of such a method of prevention has been started. We believe that in Ukraine there is an urgent need and all possibilities to solve this problem. Key words: ovarian cancer, preventive measures, opportunistic salpingectomy.


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