Massively Parallel Sequencing-Based Clonality Analysis of Synchronous Endometrioid Endometrial and Ovarian Carcinomas

Schultheis, Anne M.; Ng, Charlotte K.Y.; Filippo, Maria Rosaria De; Piscuoglio, Salvatore; Macedo, Gabriel S.; Gatius, Sònia; Mies, Belén Pérez; Soslow, Robert A.; Lim, Raymond S.; Viale, Agnès; Huberman, Kety; Palacios, Jose C.; Reis‐Filho, Jorge S.; Matías‐Guiu, Xavier; Weigelt, Britta

doi:10.1093/jnci/djv427

Cited by 196 publications

(216 citation statements)

References 41 publications

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“…Specifically, we found that 72% of EC cases and 70% of ovarian cancer cases were classified as FIGO stage I (13). Others have confirmed these findings by subjecting cancer tissue from five SEOC cases to whole-exome massively parallel sequencing, demonstrating that the endometrial and ovarian tumor cells displayed strikingly similar repertoires of somatic mutations and gene copy number alterations in all investigated cases (14). These data suggest that in women with SEOC, the endometrium and the ovary represent microenvironmentcompatible sites with preferential dissemination of tumor cells.…”

Section: Discussionsupporting

confidence: 76%

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Synchronous Endometrial and Ovarian Cancer in Young Women: Case Report and Review of the Literature

Doğan

Schultheis

Rezniczek

et al. 2017

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Abstract. Background: Young women with endometrial cancer (EC) have an increased risk of synchronous ovarian cancer. The prognosis of women with synchronous endometrial and ovarian cancer (SEOC) is good. A high proportion of affected women have hereditary non-polyposis colon cancer syndrome (HNPCCEndometrial cancer (EC) is the most common female pelvic malignancy with a life-time risk of 4% (1). It is usually diagnosed at an early stage and has a good prognosis accounting for only 2% of cancer-related deaths (1, 2). The most common age at the time of diagnosis is between 65 and 75 years with a mean age of 69 years (3). However, young women may also be affected by EC. Specifically, around 10% of women diagnosed with EC are <50 years of age with a range of 7 to 20% reported in the literature (1-4). This subset of women with EC is characterized by an elevated risk of synchronous ovarian cancer and an increased prevalence of hereditary non-polyposis colon cancer syndrome (HNPCC). This has important consequences for the management, prognosis, and genetic counselling of young women with EC.In the general population of women with EC, synchronous ovarian cancer is a rare finding. In a Surveillance, Epidemiology, and End Results Program (SEER) database analysis of 56986 women with ovarian cancer, for example, Williams et al. identified 1709 (3%) cases of synchronous endometrial and ovarian cancer (SEOC) (5). Young women with EC, however, have a significantly higher risk of SEOC with a range of 11 to 29% reported in the literature (4, 6-11). The typical histology of SEOC is endometrioid adenocarcinoma in both the endometrium and the ovary, which is found in >70% of cases (12). Based on this high rate of histological congruence among SEOC cases, a monoclonal origin has been suggested (13). Specifically, 969

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Section: Discussionsupporting

confidence: 76%

“…the endometrium and the ovary, with a limited capacity for further dissemination (13). Others have confirmed a high rate of monoclonality among SEOC cases (14).…”

mentioning

confidence: 96%

Synchronous Endometrial and Ovarian Cancer in Young Women: Case Report and Review of the Literature

Doğan

Schultheis

Rezniczek

et al. 2017

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“…Interestingly, we were able to perform exome sequencing analysis in the 3 different areas of the primary tumor and in 1 area of the ovarian mass in 1 case. Our results confirmed a pattern of branched evolution with a significant number of ubiquitous mutations, but also private mutations from different areas of the primary tumor and the ovarian metastasis [13].…”

Section: Next-generation Sequencing Confirms That Ec Follows Branchedsupporting

confidence: 82%

Tumor Heterogeneity in Endometrial Carcinoma: Practical Consequences

Gatius¹,

Cuevas²,

Fernández³

et al. 2017

Pathobiology

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Endometrial carcinoma (EC) shows intertumor heterogeneity, with several different histologic types differing in their morphologic and molecular features. There is also intratumoral morphologic heterogeneity, with different neoplastic cell components within the same tumor, with different morphologic and molecular features. In this article, we discuss the consequences of tumor heterogeneity in EC at the morphologic and molecular levels, by describing some illustrative examples produced by the research team. They are (1) morphologic heterogeneity in conventional EC and mixed tumors, (2) EC with microsatellite instability, (3) branched evolution as shown by exome sequencing analysis, (4) morphologic, molecular, and metabolomic differences between the tumor surface and myometrial invasion front, (5) tumor heterogeneity at the microenviromental level, (6) the sensitivity of endometrial aspirates to detect tumor heterogeneity in EC, and (7) sampling strategies to detect tumor heterogeneity in hysterectomy specimens. Tumor heterogeneity may have an important clinical impact, since it can be challenging to identify minor tumor cell populations that may have an impact on diagnosis, prognosis, and therapeutic decisions for patients with EC.

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“…Recent preliminary genetic studies suggest a clonal relationship between the two lesions. Given the non-aggressive course seen in many patients, this might mean that malignant tissue arises in the endometrium in these cases and reaches the ovary by transtubal retrograde flow [7]. Immunohistochemically, ovarian ECs express cytokeratin 7 (CK7), paired box 8 (PAX8), estrogen receptors (ERs) and progesterone receptors (PRs).…”

Section: Endometrioid Carcinomamentioning

confidence: 99%

Recommendations for biomarker testing in epithelial ovarian cancer: a National Consensus Statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology

Oaknin

Guarch²,

Barretina-Ginesta

et al. 2017

Clin Transl Oncol

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Because of advances in the understanding of histological and molecular characteristics in ovarian cancer, it is now possible to recognize the existence of five subtypes, which in turn has allowed a more refined therapeutic approach and better design of clinical trials. Each of these five subtypes has specific histological features and a particular biomarker expression, as well as mutations in different genes, some of which have prognostic and predictive value. CA125 and HE4 are examples of ovarian cancer biomarkers used in the diagnosis and follow-up of these malignancies. Currently, somatic or germinal mutations on BRCA1 and BRCA2 genes are the most important biomarkers in epithelial ovarian cancer having prognostic and predictive value. This article will review the histological and molecular characteristics of the five subtypes of ovarian cancer, describing the most important biomarkers and mutations that can guide in diagnosis, screening and tailored treatment strategy.

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Massively Parallel Sequencing-Based Clonality Analysis of Synchronous Endometrioid Endometrial and Ovarian Carcinomas

Cited by 196 publications

References 41 publications

Synchronous Endometrial and Ovarian Cancer in Young Women: Case Report and Review of the Literature

Synchronous Endometrial and Ovarian Cancer in Young Women: Case Report and Review of the Literature

Tumor Heterogeneity in Endometrial Carcinoma: Practical Consequences

Recommendations for biomarker testing in epithelial ovarian cancer: a National Consensus Statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology

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