Demographic, Clinical, and Prognostic Factors of Ovarian Clear Cell Adenocarcinomas According to Endometriosis Status

Schnack, Tine Henrichsen; Høgdall, Estrid; Thomsen, Lotte; Høgdall, Claus

doi:10.1097/igc.0000000000001102

Cited by 11 publications

(7 citation statements)

References 21 publications

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“…OCCC shows distinct morphologic features from other histotypes (i.e., highgrade serous, endometrioid, or mucinous carcinomas), that are tubulocystic, papillary, and solid architecture and glycogencontaining clear cells sometimes appearing as so-called hobnail cells. OCCCs are closely associated with ovarian and pelvic endometriosis from which they are thought to arise (3). Recurrence is not infrequent after surgery and platinum-based treatment and occurs in ∼30% of OCCC patients diagnosed at stage I or II (2,4).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of IGF2BP3 as a Potential Oncogene in Ovarian Clear Cell Carcinoma

et al. 2020

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Ovarian Clear Cell Carcinoma (OCCC) displays distinctive clinical and molecular characteristics and confers the worst prognosis among all ovarian carcinoma histotypes when diagnosed at advanced stage, because of the lack of effective therapy. IGF2BP3 is an RNA binding protein that modulates gene expression by post-transcriptional action. In this study, we investigated the roles of IGF2BP3 in the progression of OCCC. We used 328 OCCCs from the AOVT (the Alberta Ovarian Tumor Type study) and the COEUR (the Canadian Ovarian Experimental Unified Resource) cohorts to elucidate the associations between IGF2BP3 expression and clinicopathological parameters, with positive IGF2BP3 expression defined as diffuse block staining, being more frequently observed at stage III (P = 0.0056) and significantly associated with unfavorable overall survival (HR = 1.59, 95% CI 1.09-2.33) in multivariate analysis. IGF2BP3 mRNA gene expression was markedly increased in OCCC cell lines compared to normal tissues such as ovarian surface epithelium. We chose two IGF2BP3-overexpressing cell lines ES2 and OVMANA for in vitro and in vivo knockdown experiments. The proliferation and viability of both cell lines were significantly inhibited by two IGF2BP3 siRNAs and similar suppression was observed in cell migration and invasion by Wound Healing and Transwell assays. The percentage of apoptotic cancer cells was enhanced by both IGF2BP3 siRNAs. In vivo experiments showed significantly reduced sizes of tumors when treated with IGF2BP3 siRNA compared to controls. Furthermore, cancer metastasis-indicators MMP2 and MMP9 proteins were down-regulated. In conclusion, our study shows that IGF2BP3 expression is a promising biomarker for prognostication of women diagnosed with OCCC with multiple effects on key cell functions, supporting its role as an important cellular regulator with potential oncogenic activity, and as a potential target for future intervention strategies.

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Section: Introductionmentioning

confidence: 99%

Overexpression of IGF2BP3 as a Potential Oncogene in Ovarian Clear Cell Carcinoma

et al. 2020

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“…So far, most of the studies that have investigated the prognostic role of endometriosis in the context of EAOC have included multiple histological types, while OCCC only consisted a small subgroup of the subjects [ 14 ]. Some studies precluded other subtypes but included OCCC mixed with other histological types such as serous carcinoma [ 15 ]. Owing to heterogeneity with respect to histological subtypes of EAOCs, the results of these studies should be interpreted with caution.…”

Section: Introductionmentioning

confidence: 99%

Endometriosis does not confer improved prognosis in ovarian clear cell carcinoma: a retrospective study at a single institute

et al. 2018

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BackgroundConsidered as the precursor lesion of a subset of ovarian clear cell carcinoma (OCCC), the prognostic role of endometriosis in OCCC patients remains controversial. This study aimed to investigate the prognostic role of coexisting endometriosis in the survival of patients with OCCC, and also sought to identify other prognostic factors.ResultsA total of 125 patients were diagnosed with OCCC during the study period. Of these, 55 (44.0%) patients had coexisting endometriosis. Patients with endometriosis were younger (p = 0.030), had smaller tumor diameter (p = 0.005) and lower preoperative CA125 levels (p = 0.005). More patients with endometriosis had International Federation of Gynecology and Obstetrics (FIGO) stage I disease (83.6% vs. 51.4%, p = 0.000) and exhibited sensitivity to platinum-based regimen (89.6% vs. 66.7%, p = 0.003). Univariate and multivariate analysis revealed that coexisting endometriosis was not a predictor of 5-year overall survival (OS) or progression-free survival (PFS) of OCCC patients. For OS, chemosensitivity was the only useful prognostic factor (Hazards ratio (HR) 109.33, 95% Confidence Interval (CI) 23.46–511.51; p = 0.000). For PFS, the useful prognostic factors were ascites (HR 2.78, 95% CI 1.21–6.47; p = 0.016), FIGO stage (HR 1.61, 95% CI 1.04–2.49; p = 0.033), and chemosensitivity (HR 101.60, 95% CI 29.45–350.49; p = 0.000). Moreover, higher FIGO stage was the only risk factor for resistance to platinum-based chemotherapy (Exp (B) = 0.292, 95% CI 0.123–0.693; p = 0.005).ConclusionsIn this study, coexisting endometriosis was not a prognostic factor for the survival of OCCC patients. The most important predictor of both 5-year OS and PFS was chemosensitivity to platinum-based regimen, which decreased significantly with increase in FIGO stage.

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“…Patients with OCCC are more likely to be diagnosed at an early stage, with good prognosis when confined in the ovary. However, when diagnosed in advanced stages the prognosis is poor, due to resistance to chemotherapy [9,27]. OCCC incidence is also particular to geographical prevalence.…”

Section: Discussionmentioning

confidence: 99%

“…This database is a well-established compulsory national databank, which contains 97% of Danish patients diagnosed with gynecological cancer since 2005 [7,8]. The etiology is still elusive, although women with endometriosis have a higher risk of developing the disease [9]. Patients are diagnosed typically at a younger age (49-58 years old) and at early stage compared to other EOC subtypes [4][5][6]10], where stage I accounts for approximately 60% of all cases [9,10].…”

Section: Introductionmentioning

confidence: 99%

“…The etiology is still elusive, although women with endometriosis have a higher risk of developing the disease [9]. Patients are diagnosed typically at a younger age (49-58 years old) and at early stage compared to other EOC subtypes [4][5][6]10], where stage I accounts for approximately 60% of all cases [9,10]. Hence, the 5-year overall survival in this subtype can reach up to 90% when found early [4].…”

Section: Introductionmentioning

confidence: 99%

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Genomic Sub-Classification of Ovarian Clear Cell Carcinoma Revealed by Distinct Mutational Signatures

Oliveira

Schnack

Poulsen

et al. 2021

Cancers

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Ovarian clear cell carcinoma (OCCC) is characterized by dismal prognosis, partially due to its low sensitivity to standard chemotherapy regimen. It is also well-known for presenting unique molecular features in comparison to other epithelial ovarian cancer subtypes. Here, we aim to identify potential subgroups of patients in order to (1) determine their molecular features and (2) characterize their mutational signature. Furthermore, we sought to perform the investigation based on a potentially clinically relevant setting. To that end, we assessed the mutational profile and genomic instability of 55 patients extracted from the Gynecologic Cancer Database (DGCD) by using a panel comprised of 409 cancer-associated genes and a microsatellite assay, respectively; both are currently used in our routine environment. In accordance with previous findings, ARID1A and PIK3CA were the most prevalent mutations, present in 49.1% and 41.8%, respectively. From those, the co-occurrence of ARID1A and PIK3CA mutations was observed in 36.1% of subjects, indicating that this association might be a common feature of OCCC. The microsatellite instability frequency was low across samples. An unbiased assessment of signatures identified the presence of three subgroups, where “PIK3CA” and “Double hit” (with ARID1A and PIK3CA double mutation) subgroups exhibited unique signatures, whilst “ARID1A” and “Undetermined” (no mutations on ARID1A nor PIK3CA) subgroups showed similar profiles. Those differences were further indicated by COSMIC signatures. Taken together, the current findings suggest that OCCC presents distinct mutational landscapes within its group, which may indicate different therapeutic approaches according to its subgroup. Although encouraging, it is noteworthy that the current results are limited by sample size, and further investigation on a larger group would be crucial to better elucidate them.

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Demographic, Clinical, and Prognostic Factors of Ovarian Clear Cell Adenocarcinomas According to Endometriosis Status

Cited by 11 publications

References 21 publications

Overexpression of IGF2BP3 as a Potential Oncogene in Ovarian Clear Cell Carcinoma

Overexpression of IGF2BP3 as a Potential Oncogene in Ovarian Clear Cell Carcinoma

Endometriosis does not confer improved prognosis in ovarian clear cell carcinoma: a retrospective study at a single institute

Genomic Sub-Classification of Ovarian Clear Cell Carcinoma Revealed by Distinct Mutational Signatures

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