Molecular profiling and molecular classification of endometrioid ovarian carcinomas

Cybulska, Paulina; Paula, Arnaud Da Cruz; Tseng, Jill; Leitao, Mario M.; Bashashati, Ali; Huntsman, David G.; Nazeran, Tayyebeh M.; Aghajanian, Carol; Abu‐Rustum, Nadeem R.; DeLair, Deborah F.; Shah, Sohrab P.; Weigelt, Britta

doi:10.1016/j.ygyno.2019.07.012

Cited by 62 publications

(75 citation statements)

References 39 publications

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“…25 Recently, KRAS mutation was found in 42% of EC. 24 Although KRAS is the most frequently mutated oncogene in human cancers, no therapeutic agent directly targeting RAS has yet been approved. Our results show that KRAS was amplified in 44.4% of HGSC, and it was reported to be significantly locally amplified in TCGA.…”

Section: Discussionmentioning

confidence: 99%

Clinical implications of next‐generation sequencing‐based panel tests for malignant ovarian tumors

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Clinical implications of next‐generation sequencing‐based panel tests for malignant ovarian tumors

et al. 2020

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“…Based on a combination of mutations in POLE , expression of p53 and MMR protein expression, EOC could thus be classified into four groups: POLE mutated, MMR abnormal, p53 abnormal, and Nonspecial Type (NST, those without POLE mutations, MMRD or p53 abnormal expression). According to previous studies [ 79 , 80 ] and the results of the RECLAMO series (manuscript in preparation), the frequency of the four molecular groups was: 58%–61% NST, 11%–24% p53 abnormal, 8%–19% MMR abnormal, and 3%–10% POLE mutated. Interestingly, the frequency of POLE mutated and MMR abnormal tumours was lower in EOC than in EEC.…”

Section: Endometrioid Ovarian Carcinoma (Eoc)mentioning

confidence: 71%

“…This classification could have important prognostic and therapeutic implications. Thus, no deaths were observed among POLE mutated tumour in these series [ 79 , 80 ], and the use of immunotherapy should be an option in POLE mutated and MMR abnormal tumours.…”

Section: Endometrioid Ovarian Carcinoma (Eoc)mentioning

confidence: 99%

Morphological and molecular heterogeneity of epithelial ovarian cancer: Therapeutic implications

Romero

Leskelä

Mies

et al. 2020

European Journal of Cancer Supplements

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Ovarian epithelial cancer (OEC) is the most lethal gynecologic malignancy. Despite current chemotherapeutic and surgical options, this high lethality can be attributed to multiple factors, including late-stage presentation. In order to optimize OEC treatment, it is important to highlight that it is composed of five main subtypes: high-grade serous ovarian carcinoma (HGSOC), low-grade serous ovarian carcinoma (LGSOC), endometrioid ovarian carcinoma (EOC), ovarian clear cell carcinoma (CCOC), and mucinous ovarian carcinoma (MOC). These subtypes differ in their precursor lesions, as well as in epidemiological, morphological, molecular and clinical features. OEC is one of the tumours in which most pathogenic germline mutations have been identified. Accordingly, up to 20% OC show alterations in BRCA1/2 genes, and also, although with a lower frequency, in other low penetrance genes associated with homologous recombination deficiency (HRD), mismatch repair genes (Lynch syndrome) and TP53 . The most important prognostic factor is the 2014 FIGO staging, while older age is also associated with worse survival. HGSOC in all stages and CCC and MOC in advanced stages have the worse prognosis among histological types. Molecular markers have emerged as prognostic factors, particularly mutations in BRCA1/2, which are associated with a better outcome. Regarding treatment, whereas a proportion of HGSOC is sensible to platinum-based treatment and PARP inhibitors due to HRD, the rest of the histological types are relatively chemoresistant. New treatments based in specific molecular alterations are being tested in different histological types. In addition, immunotherapy could be an option, especially for EOC carrying mismatch repair deficiency or POLE mutations.

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“…This also highlights the importance of histotypebased survival analyses. PIK3CA is frequently mutated in ovarian EC (47). Few studies have evaluated PIK3CA in view of prognosis for ovarian EC.…”

Section: Discussionmentioning

confidence: 99%

Validation of Novel Prognostic Biomarkers for Early-Stage Clear-Cell, Endometrioid and Mucinous Ovarian Carcinomas Using Immunohistochemistry

et al. 2020

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Early-stage (I and II) ovarian carcinoma patients generally have good prognosis. Yet, some patients die earlier than expected. Thus, it is important to stratify early-stage patients into risk groups to identify those in need of more aggressive treatment regimens. The prognostic value of 29 histotype-specific biomarkers identified using RNA sequencing was evaluated for early-stage clear-cell (CCC), endometrioid (EC) and mucinous (MC) ovarian carcinomas (n = 112) using immunohistochemistry on tissue microarrays. Biomarkers with prognostic significance were further evaluated in an external ovarian carcinoma data set using the web-based Kaplan-Meier plotter tool. Here, we provide evidence of aberrant protein expression patterns and prognostic significance of 17 novel histotype-specific prognostic biomarkers [10 for CCC (ARPC2, CCT5, GNB1, KCTD10, NUP155, RPL13A, RPL37, SETD3, SMYD2, TRIO), three for EC (CECR1, KIF26B, PIK3CA), and four for MC (CHEK1, FOXM1, KIF23, PARPBP)], suggesting biological heterogeneity within the histotypes. Combined predictive models comprising the protein expression status of the validated CCC, EC and MC biomarkers together with established clinical markers (age, stage, CA125, ploidy) improved the predictive power in comparison with models containing established clinical markers alone, further strengthening the importance of the biomarkers in ovarian carcinoma. Further, even improved predictive powers were demonstrated when combining these models with our previously identified prognostic biomarkers PITHD1 (CCC) and GPR158 (MC). Moreover, the proteins demonstrated improved risk prediction of CCC-, EC-, and MC-associated ovarian carcinoma survival. The novel histotype-specific prognostic biomarkers may not only improve prognostication and patient stratification of early-stage ovarian carcinomas, but may also guide future clinical therapy decisions.

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Molecular profiling and molecular classification of endometrioid ovarian carcinomas

Cited by 62 publications

References 39 publications

Clinical implications of next‐generation sequencing‐based panel tests for malignant ovarian tumors

Clinical implications of next‐generation sequencing‐based panel tests for malignant ovarian tumors

Morphological and molecular heterogeneity of epithelial ovarian cancer: Therapeutic implications

Validation of Novel Prognostic Biomarkers for Early-Stage Clear-Cell, Endometrioid and Mucinous Ovarian Carcinomas Using Immunohistochemistry

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