Quantitative assesment of coexpression of cytokeratins and mesenchimal cells marker vimentin in serous ovarian cancer

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.

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Abstract 2897: The metastatic potential of high-grade serous ovarian cancer cells along disease progression

10.1158/1538-7445.am2021-2897 ◽

2021 ◽

Author(s):

Sabrina J. Ritch ◽

Alicia A. Goyeneche ◽

Abu S. Noman ◽

Carlos M. Telleria

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Disease Progression ◽

Metastatic Potential ◽

Ovarian Cancer Cells ◽

High Grade ◽

Serous Ovarian Cancer

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Expression and Clinical Significance of the NCAPH, AGGF1, and FOXC2 Proteins in Serous Ovarian Cancer

Cancer Management and Research ◽

10.2147/cmar.s329688 ◽

2021 ◽

Vol Volume 13 ◽

pp. 7253-7262

Author(s):

Yingying Sun ◽

Xuan Wang ◽

Hexin Wen ◽

Bo Zhu ◽

Lan Yu

Keyword(s):

Ovarian Cancer ◽

Clinical Significance ◽

Serous Ovarian Cancer

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Progression-Mediated Changes in Mitochondrial Morphology Promotes Adaptation to Hypoxic Peritoneal Conditions in Serous Ovarian Cancer

Frontiers in Oncology ◽

10.3389/fonc.2020.600113 ◽

2021 ◽

Vol 10 ◽

Author(s):

Joseph P. Grieco ◽

Mitchell E. Allen ◽

Justin B. Perry ◽

Yao Wang ◽

Yipei Song ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Model ◽

Gynecological Cancer ◽

Metastatic Potential ◽

Adaptation To Hypoxia ◽

Mitochondrial Morphology ◽

Serous Ovarian Cancer ◽

Tumor Initiating Cells ◽

Mitochondrial Dynamic ◽

Functional Changes

Ovarian cancer is the deadliest gynecological cancer in women, with a survival rate of less than 30% when the cancer has spread throughout the peritoneal cavity. Aggregation of cancer cells increases their viability and metastatic potential; however, there are limited studies that correlate these functional changes to specific phenotypic alterations. In this study, we investigated changes in mitochondrial morphology and dynamics during malignant transition using our MOSE cell model for progressive serous ovarian cancer. Mitochondrial morphology was changed with increasing malignancy from a filamentous network to single, enlarged organelles due to an imbalance of mitochondrial dynamic proteins (fusion: MFN1/OPA1, fission: DRP1/FIS1). These phenotypic alterations aided the adaptation to hypoxia through the promotion of autophagy and were accompanied by changes in the mitochondrial ultrastructure, mitochondrial membrane potential, and the regulation of reactive oxygen species (ROS) levels. The tumor-initiating cells increased mitochondrial fragmentation after aggregation and exposure to hypoxia that correlated well with our previously observed reduced growth and respiration in spheroids, suggesting that these alterations promote viability in non-permissive conditions. Our identification of such mitochondrial phenotypic changes in malignancy provides a model in which to identify targets for interventions aimed at suppressing metastases.

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298O The clinical significance of deregulated cyclin E1 in high grade serous ovarian cancer (HGSOC)

Annals of Oncology ◽

10.1093/annonc/mdw585.002 ◽

2016 ◽

Vol 27 (suppl_9) ◽

Author(s):

D. Aziz ◽

D. Etemadmoghadam ◽

G. Au-Yeung ◽

A. Muranyi ◽

I. Gresshoff ◽

...

Keyword(s):

Ovarian Cancer ◽

Clinical Significance ◽

High Grade ◽

Serous Ovarian Cancer ◽

Cyclin E1

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Reduced Expression of NDUFS3 and Its Clinical Significance in Serous Ovarian Cancer

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e318287a90d ◽

2013 ◽

Vol 23 (4) ◽

pp. 622-629 ◽

Cited By ~ 5

Author(s):

Pei Wang ◽

Xiaodong Cheng ◽

Zhiqin Fu ◽

Caiyun Zhou ◽

Weiguo Lu ◽

...

Keyword(s):

Ovarian Cancer ◽

Clinical Significance ◽

Serous Ovarian Cancer

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

Scientific Reports ◽

10.1038/srep42929 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 29

Author(s):

Stefanie Aust ◽

Sophie Felix ◽

Katharina Auer ◽

Anna Bachmayr-Heyda ◽

Lukas Kenner ◽

...

Keyword(s):

Ovarian Cancer ◽

Tumor Cells ◽

Serous Ovarian Cancer ◽

Mhc I

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Integrated Molecular Profiling Studies to Characterize the Cellular Origins of High-Grade Serous Ovarian Cancer

10.1101/330597 ◽

2018 ◽

Cited By ~ 9

Author(s):

Kate Lawrenson ◽

Marcos A.S. Fonseca ◽

Felipe Segato ◽

Janet M. Lee ◽

Rosario I. Corona ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Cells ◽

Tumor Development ◽

Molecular Profiling ◽

High Grade ◽

Serous Ovarian Cancer ◽

Cell Of Origin ◽

Ovarian Cancers ◽

Integrative Analyses ◽

Ovarian Surface Epithelial

AbstractHistorically, high-grade serous ovarian cancers (HGSOCs) were thought to arise from ovarian surface epithelial cells (OSECs) but recent data implicate fallopian tube secretory epithelial cells (FTSECs) as the major precursor. We performed transcriptomic and epigenomic profiling to characterize molecular similarities between OSECs, FTSECs and HGSOCs. Transcriptomic signatures of FTSECs were preserved in most HGSOCs reinforcing FTSECs as the predominant cell-of-origin; though an OSEC-like signature was associated with increased chemosensitivity (Padj= 0.03) and was enriched in proliferative-type tumors, suggesting a dualistic model for HGSOC origins. More super-enhancers (SEs) were shared between FTSECs and HGSOCs than between OSECS and HGSOCs (P< 2.2 × 10−16). SOX18, ELF3 and EHF transcription factors (TFs) coincided with HGSOC SEs and represent putative novel drivers of tumor development. Our integrative analyses support a predominantly fallopian origin for HGSOCs and indicate tumorigenesis may be driven by different TFs according to cell-of-origin.

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