Genomic and Molecular Abnormalities in Gynecologic Clear Cell Carcinoma

Marks, Eric I; Brown, Victoria S; Dizon, Don S.

doi:10.1097/coc.0000000000000641

Cited by 14 publications

(14 citation statements)

References 70 publications

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“…OCCC lesions tend to be positive for CK7 and negative for CK20, ER, PR, WT-1, and p53(10, 25). Testing negative for α-fetoprotein and CD10 can be used to exclude yolk cell tumors and renal cell carcinoma (26). We analyzed immunohistochemical results of our patients, and 55%(11/20) of them had positive HNF1β and negative WT-1, ER and PR.…”

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics and Prognosis of Ovarian Clear Cell Carcinoma: A 10-Year Retrospective Study

Zhu

Zhu²,

Qian³

et al. 2020

Preprint

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Background Ovarian clear cell carcinoma (OCCC) is a special pathological type of epithelial ovarian carcinoma (EOC), we conducted this research in order to investigate the clinical characteristics and outcomes of OCCC and to provide additional supporting evidence to aid in the clinical diagnosis and management. Methods This was a retrospective study investigating the clinical characteristics and survival outcomes of 87 patients with OCCC treated at our center between January 2010 and March 2020. Survival analysis was also performed on 179 patients with OCCC obtained from the Surveillance, Epidemiology and End Results (SEER) cancer registry database. Results The median age of participants was 49.28 ± 9.8 years old, with 74.71% diagnosed at early stage. Median CA125 level was 607.26 IU/mL, with 23.94% having normal CA125 levels. 16 patients (18.39%) had co-existing endometriosis and 8 patients (9.2%) developed venous thromboembolism (VTE). There were 5 patients received suboptimal cytoreduction. 67 patients (77.01%) underwent lymphadenectomy, and only 3 (4.48%) were found to have positive lymph nodes. Patients diagnosed at an early stage had higher 3-year overall survival (OS) and progression-free survival (PFS) rates than those with advanced stage OCCC. CA199 (P = 0.025) and ascites (P = 0.001) were significantly associated with OS, while HE4 (P = 0.027) and ascites (P = 0.001) were significantly associated with PFS. Analysis of data from the SEER database showed that positive lymph nodes is also an independent prognostic factor for OS (P = 0.001). Conclusions OCCC often presents at an early stage and young age with a mildly elevated CA125. CA199, HE4, massive ascites and positive lymph node are independent prognostic factors.

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Section: Discussionmentioning

confidence: 99%

Clinical Characteristics and Prognosis of Ovarian Clear Cell Carcinoma: A 10-Year Retrospective Study

Zhu

Zhu²,

Qian³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…OCCC lesions tend to be positive for CK7 and negative for CK20, ER, PR, WT-1, and p53 (10,25). Testing negative for α-fetoprotein and CD10 can be used to exclude yolk cell tumors and renal cell carcinoma (26). We analyzed immunohistochemical results of our patients, and 55%(11/20) of them had positive HNF1β and negative WT-1, ER and PR.…”

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics and Prognosis of Ovarian Clear Cell Carcinoma: A 10-Year Retrospective Study

Zhao¹,

Zhu²,

Zhu³

et al. 2020

Preprint

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Background Ovarian clear cell carcinoma (OCCC) is a special pathological type of epithelial ovarian carcinoma (EOC), we conducted this research in order to investigate the clinical characteristics and outcomes of OCCC and to provide additional supporting evidence to aid in the clinical diagnosis and management. Methods This was a retrospective study investigating the clinical characteristics and survival outcomes of 87 patients with OCCC treated at our center between January 2010 and March 2020. Survival analysis was also performed on 179 patients with OCCC obtained from the Surveillance, Epidemiology and End Results (SEER) cancer registry database. Results The median age of participants was 49.28 ± 9.8 years old, with 74.71% diagnosed at early stage. Median CA125 level was 607.26 IU/mL, with 23.94% having normal CA125 levels. 16 patients (18.39%) had co-existing endometriosis and 8 patients (9.2%) developed venous thromboembolism (VTE). There were 5 patients received suboptimal cytoreduction. 67 patients (77.01%) underwent lymphadenectomy, and only 3 (4.48%) were found to have positive lymph nodes. Patients diagnosed at an early stage had higher 3-year overall survival (OS) and progression-free survival (PFS) rates than those with advanced stage OCCC. CA199 (P = 0.025) and ascites (P = 0.001) were signi cantly associated with OS, while HE4 (P = 0.027) and ascites (P = 0.001) were signi cantly associated with PFS. Analysis of data from the SEER database showed that positive lymph nodes is also an independent prognostic factor for OS (P = 0.001). Conclusions OCCC often presents at an early stage and young age with a mildly elevated CA125. CA199, HE4, massive ascites and positive lymph node are independent prognostic factors.

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“…Clear-cell ovarian cancers display mutations in the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex genes, the PI3K/Akt signaling pathway, and the receptor tyrosine kinase (RTK)/Ras signaling pathway in nearly 50%, 40%, and 29% of clear-cell ovarian cancers, respectively [10,24,25]. Among the SWI/SNF subunits, ARID1A is the most frequently mutated gene, detected in 40% to 67% of clear-cell ovarian cancers [26,27].…”

Section: Histologic Subtypes Of Ovarian Cancer Molecular Correlatesmentioning

confidence: 99%

“…Two examples are the phase II ARIEL3 trial with rucaparib and the NOVA trial with niraparib. The NOVA trial showed that niraparib was effective in patients with platinum-sensitive ovarian cancer, demonstrating that PARP inhibitors are effective in carriers of mutations other than BRCA1 and BRCA2 [24]. Efforts are also underway to analyze the combined use of drugs with different effects.…”

Section: Brcaness: Definition and Treatment Implicationsmentioning

confidence: 99%

The Landscape and Therapeutic Implications of Molecular Profiles in Epithelial Ovarian Cancer

Dion

Carton

Jaillard

et al. 2020

JCM

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Epithelial ovarian cancer (EOC) affects 43,000 women worldwide every year and has a five-year survival rate of 30%. Mainstay treatment is extensive surgery and chemotherapy. Outcomes could be improved by molecular profiling. We conducted a review of the literature to identify relevant publications on molecular and genetic alterations in EOC. Approximately 15% of all EOCs are due to BRCA1 or BRCA2 mutations. Four histologic subtypes characterized by different mutations have been described: serous, endometrioid, mucinous, and clear-cell. Between 20–30% of high-grade serous EOCs have a BRCA mutation. Tumors with BRCA mutations are unable to repair double-strand DNA breaks, making them more sensitive to platinum-based chemotherapy and to PolyAdenosine Diphosphate-Ribose Polymerase (PARP) inhibitors. Olaparib is a PARP inhibitor with proven efficacy in BRCA-mutated ovarian cancer, but its effectiveness remains to be demonstrated in tumors with a BRCAness (breast cancer) profile (i.e., also including sporadic tumors in patients with deficient DNA repair genes). A universally accepted molecular definition of BRCAness is required to identify optimal theranostic strategies involving PARP inhibitors. Gene expression analyses have led to the identification of four subgroups of high-grade serous EOC: mesenchymal, proliferative, differentiated, and immunoreactive. These subtypes are not mutually exclusive but are correlated with prognosis. They are not yet used in routine clinical practice. A greater understanding of EOC subtypes could improve patient management.

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Genomic and Molecular Abnormalities in Gynecologic Clear Cell Carcinoma

Cited by 14 publications

References 70 publications

Clinical Characteristics and Prognosis of Ovarian Clear Cell Carcinoma: A 10-Year Retrospective Study

Clinical Characteristics and Prognosis of Ovarian Clear Cell Carcinoma: A 10-Year Retrospective Study

Clinical Characteristics and Prognosis of Ovarian Clear Cell Carcinoma: A 10-Year Retrospective Study

The Landscape and Therapeutic Implications of Molecular Profiles in Epithelial Ovarian Cancer

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