Clear cell carcinoma of the ovary: Epidemiology, pathological and biological features, treatment options and clinical outcomes

Gadducci, Angiolo; Multinu, Francesco; Cosio, Stefania; Carinelli, Silvestro; Ghioni, Mariacristina; Aletti, Giovanni

doi:10.1016/j.ygyno.2021.06.033

Cited by 76 publications

(94 citation statements)

References 58 publications

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“…This result is consistent with the prevalence of ARID1A mutations, which is normally in the range between 30-70% of OCCC cases 2,5,15,49,51 . Notably, we found that loss of ARID1A occurred more frequently in patients with endometriosis found during pathological diagnosis, and also had a tendency to present at lower stages (Table 1), which is consistent with the fact that ARID1A mutations are frequently associated with endometriosis 1,2,52–57 .…”

Section: Resultssupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

“…OCCC is characterized by a specific subset of genetic mutations, the most frequent one being inactivating mutations (protein loss) of ARID1A, which is found in approximately 50% of patients [1][2][3][4][5] . ARID1A is a member of the SWI/SNF (SWIft/Sucrose Non-Fermentable) complex of chromatin remodelers and is considered a tumor suppressor 5 .…”

Section: Introductionmentioning

confidence: 99%

“…Ovarian clear cell carcinoma (OCCC) is an indolent form of ovarian cancer associated with a poor prognosis. The principal reason for such a dismal prognosis is resistance to standard-of-care chemotherapy used in general for ovarian carcinomas, including taxol- and platinum-based agents 1 . OCCC is characterized by a specific subset of genetic mutations, the most frequent one being inactivating mutations (protein loss) of ARID1A , which is found in approximately 50% of patients 1–5 .…”

Section: Introductionmentioning

confidence: 99%

“…The principal reason for such a dismal prognosis is resistance to standard-of-care chemotherapy used in general for ovarian carcinomas, including taxol- and platinum-based agents 1 . OCCC is characterized by a specific subset of genetic mutations, the most frequent one being inactivating mutations (protein loss) of ARID1A , which is found in approximately 50% of patients 1–5 . ARID1A is a member of the SWI/SNF (SWIft/Sucrose Non-Fermentable) complex of chromatin remodelers and is considered a tumor suppressor 5 .…”

Section: Introductionmentioning

confidence: 99%

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GLS1 is a protective factor rather than a molecular target in ARID1A-mutated ovarian clear cell carcinoma

Clemente

Nelson

Erickson

et al. 2021

Preprint

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Targeting glutamine metabolism has emerged as a novel therapeutic strategy for several human cancers, including ovarian cancer. The primary target of this approach is kidney isoform of glutaminase (Glutaminase 1, GLS1), a key enzyme in glutamine metabolism that is overexpressed in several human cancers. A first-in-class inhibitor of GLS1, called CB839 (Telaglenastat), has been investigated in several clinical trials, with promising results. The first clinical trial of CB839 in platinum resistant ovarian cancer patients is forthcoming. ARID1A-mutated ovarian clear cell carcinoma (OCCC) is a relatively indolent and also chemoresistant ovarian cancer histotype. In OCCC derived cells in vitro as well in mouse models, loss of ARID1A leads to upregulation of GLS1. Thus, targeting of GLS1 with CB839 has been suggested as a targeted approach for OCCC patients with tumors harboring ARID1A-mutations. Here, we investigated whether GLS1 is differentially expressed between OCCC patients whose tumors are ARID1A positive and patients whose tumors are ARID1A negative. If validated, testing of ARID1A would provide a new time and cost-effective predictive biomarker for stratification of OCCC patients based on the likelihood to respond to CB839 treatment. We found that in clinical specimens of OCCC GLS1 overexpression is not correlated to ARID1A loss; on the contrary, this overexpression is actually associated with better outcome. Our findings suggest that in OCCC, GLS1 may be a protective factor and that caution should be taken when considering the use of CB839 to treat OCCC patients.

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Section: Resultssupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

GLS1 is a protective factor rather than a molecular target in ARID1A-mutated ovarian clear cell carcinoma

Clemente

Nelson

Erickson

et al. 2021

Preprint

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The splicing factor DHX38/PRP16 is required for ovarian clear cell carcinoma tumorigenesis, as revealed by a CRISPR‐Cas9 screen

et al. 2022

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Certain cancers, such as ovarian clear cell carcinoma (OCCC), display high levels of genetic variation between patients, making it difficult to develop effective therapies. In order to identify novel genes critical to OCCC growth, we carried out a comprehensive CRISPR‐Cas9 knockout screen against cell growth using an OCCC cell line and a normal ovarian surface epithelium cell line. We identified the gene encoding DHX38/PRP16, an ATP‐dependent RNA helicase involved in splicing, as critical for the growth and tumorigenesis of OCCC. DHX38/PRP16 knockdown in OCCC cells, but not normal cells, induces apoptosis and impairs OCCC tumorigenesis in a mouse model. Our results suggest that DHX38/PRP16 may play a role in OCCC tumorigenesis and could potentially be a promising therapeutic target.

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Development and external validation of nomograms for predicting individual survival in patients with ovarian clear cell carcinoma

Liu

Ying

et al. 2023

Cancer Medicine

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Purpose Ovarian clear cell carcinoma (OCCC) is a distinct and highly malignant subtype of ovarian cancer with high individual heterogeneity in survival that requires specific prognostic predictive tools. Thus, this study aimed to construct and validate nomograms for predicting individual survival in OCCC patients. Methods In total, 91 patients with OCCC who were diagnosed and treated at Renji Hospital between 2010 and 2020 were extracted as the training cohort, then 86 patients from the First Affiliated Hospital of USTC were used as the external validation cohort. Prognostic factors that affect survival were identified using least absolute shrinkage and selection operator regression. Nomograms of progression‐free survival (PFS) and overall survival (OS) were then established with the Cox regression model and the performance was subsequently evaluated using the concordance index (C‐index), calibration plots, decision curve analysis (DCA), and risk subgroup classification. Results Advanced tumor, ascites of >400 mL, lymph node‐positive, CA199 of >142.3 IU/mL, and fibrinogen of >5.36 g/L were identified as risk factors for OS while advanced tumor, ascites of >400 mL, lymph node‐positive, and fibrinogen of >5.36 g/L were risk factors for PFS. The C‐indexes for the OS and PFS nomograms were 0.899 and 0.731 in the training cohort and 0.804 and 0.787 in the validation cohort, respectively. The calibration plots showed that nomograms could provide better consistency in predicting patient survival than the FIGO staging system. DCA also demonstrated that nomograms were more clinically beneficial than the FIGO staging system. Additionally, patients could be classified into two risk groups based on scores using nomograms, with significant survival differences. Conclusions We developed nomograms that could more objectively and reliably predict the individual survival of patients with OCCC compared with the FIGO staging system. These tools might assist in clinical decision‐making and management of patients with OCCC to improve their survival outcomes.

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Clear cell carcinoma of the ovary: Epidemiology, pathological and biological features, treatment options and clinical outcomes

Cited by 76 publications

References 58 publications

GLS1 is a protective factor rather than a molecular target in ARID1A-mutated ovarian clear cell carcinoma

GLS1 is a protective factor rather than a molecular target in ARID1A-mutated ovarian clear cell carcinoma

The splicing factor DHX38/PRP16 is required for ovarian clear cell carcinoma tumorigenesis, as revealed by a CRISPR‐Cas9 screen

Development and external validation of nomograms for predicting individual survival in patients with ovarian clear cell carcinoma

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