scholarly journals Tumor core biopsies adequately represent immune microenvironment of high-grade serous carcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Olivia D. Lara ◽  
Santhoshi Krishnan ◽  
Zhihui Wang ◽  
Sara Corvigno ◽  
YanPing Zhong ◽  
...  
Keyword(s):  
Tissue Sample ◽  
Serous Carcinoma ◽  
Specific Cell ◽  
High Grade ◽  
Longitudinal Assessment ◽  
Substantial Impact ◽  
Major Interest ◽  
Cancer Types ◽  
Detection Of Biomarkers ◽  
Cluster Of Differentiation

AbstractThe prognostic and therapeutic value of the tumor microenvironment (TME) in various cancer types is of major interest. Characterization of the TME often relies on a small representative tissue sample. However, the adequacy of such a sample for assessing components of the TME is not yet known. Here, we used immunohistochemical (IHC) staining and 7-color multiplex staining to evaluate CD8 (cluster of differentiation 8), CD68, PD-L1 (programmed death-ligand 1), CD34, FAP (fibroblast activation protein), and cytokeratin in 220 tissue cores from 26 high-grade serous ovarian cancer samples. Comparisons were drawn between a larger tumor specimen and smaller core biopsies based on number and location (central tumor vs. peripheral tumor) of biopsies. Our analysis found that the correlation between marker-specific cell subsets in larger tumor versus smaller core was stronger with two core biopsies and was not further strengthened with additional biopsies. Moreover, this correlation was consistently strong regardless of whether the biopsy was taken at the center or at the periphery of the original tumor sample. These findings could have a substantial impact on longitudinal assessment for detection of biomarkers in clinical trials.

scholarly journals C/EBPδ demonstrates a dichotomous role in tumor initiation and promotion of epithelial carcinoma

2019 ◽  
Author(s):  
Ramlogan Sowamber ◽  
Rania Chehade ◽  
Mahmoud Bitar ◽  
Leah Dodds ◽  
Anca Milea ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Leucine Zipper ◽  
Transcriptional Factor ◽  
Serous Carcinoma ◽  
Breast Cancer Cell Lines ◽  
High Grade ◽  
Basic Leucine Zipper ◽  
Cancer Types ◽  
Consistent Function ◽  
Carcinoma Of The Ovary

AbstractC/EBPδ(CEBPD), a gene part of the highly conserved basic-leucine zipper (b-ZIP) domain of transcriptional factors, is downregulated in 65% of high grade serous carcinoma of the ovary (HGSC). Overexpression ofC/EBPδin different tumors as glioblastoma and breast cancer either promotes tumor progression or inhibits growth. Despite these contradictory roles in different cancer types, we show thatC/EBPδoverexpression has a consistent function of downregulating proliferation and promoting migration in fallopian tube epithelial cells (FTE). We show that the FTE have both mesenchymal and epithelial cell characteristics. Further, our data supports a role forC/EBPδas an early regulatory transcriptional factor that promotes a mesenchymal to epithelial (MET) phenotype by upregulating E-cadherin and downregulating vimentin and N-cadherin in FTE cells. We demonstrate that overexpression ofC/EBPδin ovarian and breast cancer cell lines have consistent effects and phenotype as the FTE cells. Our findings suggest a role forC/EBPδin the early events of ovarian serous carcinogenesis which may be used to help further understand how the disease develops from a premalignant cells.

scholarly journals Targeting progesterone signaling prevents metastatic ovarian cancer

2020 ◽  
Vol 117 (50) ◽  
pp. 31993-32004
Author(s):  
Olga Kim ◽  
Eun Young Park ◽  
Sun Young Kwon ◽  
Sojin Shin ◽  
Robert E. Emerson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Deleterious Mutation ◽  
Peritoneal Metastases ◽  
Cancer Development ◽  
Serous Carcinoma ◽  
Cancer Type ◽  
High Grade ◽  
Primary Tumors ◽  
High Risk Populations ◽  
Genetic Deletion

Effective cancer prevention requires the discovery and intervention of a factor critical to cancer development. Here we show that ovarian progesterone is a crucial endogenous factor inducing the development of primary tumors progressing to metastatic ovarian cancer in a mouse model of high-grade serous carcinoma (HGSC), the most common and deadliest ovarian cancer type. Blocking progesterone signaling by the pharmacologic inhibitor mifepristone or by genetic deletion of the progesterone receptor (PR) effectively suppressed HGSC development and its peritoneal metastases. Strikingly, mifepristone treatment profoundly improved mouse survival (∼18 human years). Hence, targeting progesterone/PR signaling could offer an effective chemopreventive strategy, particularly in high-risk populations of women carrying a deleterious mutation in the BRCA gene.

Clinical Outcomes of Patients with High-Grade Ovarian Carcinoma Arising in Endometriosis Compared to Ovarian High-Grade Serous Carcinoma

2021 ◽  
Vol 19 (4) ◽  
Author(s):  
Ibrahim Yalcin ◽  
Hanifi Sahin ◽  
Mustafa Erkan Sari ◽  
Asuman Nihan Haberal ◽  
Eda Adeviye Sahin ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Clinical Outcomes ◽  
Serous Carcinoma ◽  
High Grade

scholarly journals Tumour Versus Germline BRCA Testing in Ovarian Cancer: A Single-Site Institution Experience in the United Kingdom

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 547
Author(s):  
Iolia Akaev ◽  
Siavash Rahimi ◽  
Olubukola Onifade ◽  
Francis John Edward Gardner ◽  
David Castells-Rufas ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Unknown Origin ◽  
Parp Inhibitors ◽  
Serous Carcinoma ◽  
High Grade ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Epithelial Cancers ◽  
Pathogenic Variants ◽  
Pathogenic Mutations

The aim of this audit was to evaluate the usefulness and serviceability of testing for pathogenic mutations in BRCA1 or BRCA2 (BRCA1/2) genes in ovarian cancer (OC) patients. One hundred and thirty-five patients with more common histological sub-types of OC were retrospectively identified between 2011 and 2019. The fail rate of the molecular analysis was 7.4% (10/135). One hundred and twenty-five records were evaluated: 99 (79.2%) patients had wild-type BRCA (both somatic and germline); tumour BRCA1/2 (tBRCA1/2) pathogenic mutations were found in 20 (16%) patients with distribution between BRCA1 and BRCA2 being 40% and 60%, respectively; 13 (10.4%) patients with pathogenic variants had germline mutations; and tBRCA1/2 with variant of unknown significance (VUS), in the absence of pathogenic BRCA1 or BRCA2 variants, was detected in 6 (4.8%) patients. Our data show that expanding the molecular service to the routine first-tumour testing for patients with OC will potentially increase the detection rate of BRCA mutations, thereby providing early benefits of PARP inhibitors therapy. The tumour testing service should continue to be offered to newly diagnosed patients with high-grade epithelial cancers, including high-grade serous carcinoma, but also with carcinosarcomas and poorly-differentiated metastatic adenocarcinomas of unknown origin.

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