scholarly journals The Emerging Genomic Landscape of Endometrial Cancer

2014 ◽  
Vol 60 (1) ◽  
pp. 98-110 ◽  
Author(s):  
Matthieu Le Gallo ◽  
Daphne W Bell
Keyword(s):  
Endometrial Cancer ◽  
Copy Number ◽  
Historical Context ◽  
Molecular Classification ◽  
Genomic Alterations ◽  
Current State ◽  
Genomic Landscape ◽  
The Us ◽  
Endometrial Carcinomas

AbstractBACKGROUNDEndometrial cancer is responsible for approximately 74 000 deaths annually among women worldwide. It is a heterogeneous disease comprising multiple histologic subtypes. In the US, the majority of deaths from endometrial carcinoma are attributed to the serous and endometrioid subtypes. An understanding of the fundamental genomic alterations that drive serous and endometrioid endometrial carcinomas lays the foundation for the identification of molecular markers that could improve the clinical management of patients presenting with these tumors.CONTENTWe review the current state of knowledge regarding somatic genomic alterations that occur in serous and endometrioid endometrial tumors. We present this knowledge in a historical context by reviewing the genomic alterations that studies of individual genes and proteins have identified over the past 2 decades or so. We then review very recent comprehensive and systematic surveys of genomic, exomic, transcriptomic, epigenomic, and proteomic alterations in serous and endometrioid endometrial carcinomas.SUMMARYThe recent mapping of the genomic landscape of serous and endometrioid endometrial carcinomas has produced the first comprehensive molecular classification of these tumors, which has distinguished 4 molecular subgroups: a POLE [polymerase (DNA directed), ε, catalytic subunit] ultramutated subgroup, a hypermutated/microsatellite-unstable subgroup, a copy number–low/microsatellite-stable subgroup, and a copy number–high subgroup. This molecular classification may ultimately serve to refine the diagnosis and treatment of women with endometrioid and serous endometrial tumors.

scholarly journals The TCGA Molecular Classification of Endometrial Cancer and Its Possible Impact on Adjuvant Treatment Decisions

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1478
Author(s):  
Matthias Alexa ◽  
Annette Hasenburg ◽  
Marco Johannes Battista
Keyword(s):  
Endometrial Cancer ◽  
Adjuvant Treatment ◽  
Copy Number ◽  
Histological Grade ◽  
Treatment Decision ◽  
Risk Groups ◽  
Molecular Classification ◽  
Treatment Decisions ◽  
P53 Expression

Adjuvant treatment decisions for endometrial cancer (EC) are based on stage, the histological grade of differentiation, histological subtype, and few histopathological markers. The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) identified four risk groups of EC patients using a combination of immunohistochemistry and mutation analysis: Polymerase Epsilon exonuclease domain mutated (POLE EDM), mismatch repair deficient (MMRd), p53 wild-type/copy-number-low (p53 wt), and p53-mutated/copy-number-high (p53 abn). Patients allocated to the POLE or abnormal p53 expression subtype are faced with a significantly altered outcome possibly requiring a modified adjuvant treatment decision. Within this review, we summarize the development of ProMisE, characterize the four molecular subtypes, and finally discuss its value in terms of a patient-tailored therapy in order to prevent significant under or overtreatment.

scholarly journals Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: Impact on adjuvant therapy

2019 ◽  
Vol 30 ◽  
pp. v899-v900 ◽  
Author(s):  
C.L. Creutzberg ◽  
A. Leon-Castillo ◽  
S.M. de Boer ◽  
M.E. Powell ◽  
L.R. Mileshkin ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Molecular Classification

scholarly journals A Timely Update of Immunohistochemistry and Molecular Classification in the Diagnosis and Risk Assessment of Endometrial Carcinomas

2021 ◽  
Vol 145 (11) ◽  
pp. 1367-1378
Author(s):  
Minhua Wang ◽  
Pei Hui
Keyword(s):  
Copy Number ◽  
Treatment Strategies ◽  
The United States ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Molecular Profile ◽  
Cancer Genome Atlas ◽  
Endometrial Carcinomas ◽  
Genome Atlas

Context.— Endometrial carcinoma is the most common gynecologic malignancy in the United States and has been traditionally classified based on histology. However, the distinction of certain histologic subtypes based on morphology is not uncommonly problematic, and as such, immunohistochemical study is often needed. Advances in comprehensive tumor sequencing have provided novel molecular profiles of endometrial carcinomas. Four distinct molecular subtypes with different prognostic values have been proposed by The Cancer Genome Atlas program: polymerase epsilon ultramutated, microsatellite instability hypermutated, copy number low (microsatellite stable or no specific molecular profile), and copy number high (serouslike, p53 mutant). Objective.— To discuss the utilities of commonly used immunohistochemical markers for the classification of endometrial carcinomas and to review the recent advancements of The Cancer Genome Atlas molecular reclassification and their potential impact on treatment strategies. Data Sources.— Literature review and authors' personal practice experience. Conclusions.— The current practice of classifying endometrial cancers is predominantly based on morphology. The use of ancillary testing, including immunohistochemistry, is helpful in the identification, differential diagnosis, and classification of these cancers. New developments such as molecular subtyping have provided insightful prognostic values for endometrial carcinomas. The proposed The Cancer Genome Atlas classification is poised to gain further prominence in guiding the prognostic evaluation for tailored treatment strategies in the near future.

scholarly journals Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats

2009 ◽  
Vol 16 (1) ◽  
pp. 99-111 ◽  
Author(s):  
Emma Samuelson ◽  
Carola Hedberg ◽  
Staffan Nilsson ◽  
Afrouz Behboudi
Keyword(s):  
Cell Biology ◽  
Tumor Model ◽  
Molecular Classification ◽  
Female Rats ◽  
Type I ◽  
Over Expression ◽  
Molecular Alterations ◽  
Molecular Features ◽  
Endometrial Carcinomas

Female rats of the BDII/Han inbred strain are prone to spontaneously develop endometrial carcinomas (EC) that in cell biology and pathogenesis are very similar to those of human. Human EC are classified into two major groups: Type I displays endometroid histology, is hormone-dependent, and characterized by frequent microsatellite instability and PTEN, K-RAS, and CTNNB1 (β-Catenin) mutations; Type II shows non-endometrioid histology, is hormone-unrelated, displays recurrent TP53 mutation, CDKN2A (P16) inactivation, over-expression of ERBB2 (Her2/neu), and reduced CDH1 (Cadherin 1 or E-Cadherin) expression. However, many human EC have overlapping clinical, morphologic, immunohistochemical, and molecular features of types I and II. The EC developed in BDII rats can be related to type I tumors, since they are hormone-related and histologically from endometrioid type. Here, we combined gene sequencing (Pten, Ifr1, and Ctnnb1) and real-time gene expression analysis (Pten, Cdh1, P16, Erbb2, Ctnnb1, Tp53, and Irf1) to further characterize molecular alterations in this tumor model with respect to different subtypes of EC in humans. No mutation in Pten and Ctnnb1 was detected, whereas three tumors displayed sequence aberrations of the Irf1 gene. Significant down regulation of Pten, Cdh1, p16, Erbb2, and Ctnnb1 gene products was found in the tumors. In conclusion, our data suggest that molecular features of spontaneous EC in BDII rats can be related to higher-grade human type I tumors and thus, this model represents an excellent experimental tool for research on this malignancy in human.

Knowledge-based expert systems — The State of the Art in the US

1984 ◽  
Vol 1 (2) ◽  
pp. 18-27 ◽  
Author(s):  
F. Hayes-Roth
Keyword(s):  
Expert Systems ◽  
State Of The Art ◽  
Historical Context ◽  
The State ◽  
Knowledge Systems ◽  
Future Trends ◽  
Knowledge Based ◽  
Current State ◽  
The Us

SummaryThis paper aims to describe the current state of knowledge systems technology and its commercialisation in the US. First, knowledge systems are defined and placed in a historical context. The introduction is concluded with a preview of major ideas. The paper will assess the technological state of the art and will survey the current state of commercialisation. Finally, some anticipated future trends will be discussed.

scholarly journals Mismatch repair deficiency: a step forward personalized medicine in endometrial cancer?

2016 ◽  
Vol 4 (2) ◽  
pp. 34-41
Author(s):  
Chiara Della Pepa ◽  
Susana Banerjee ◽  
Angela George
Keyword(s):  
Endometrial Cancer ◽  
Copy Number ◽  
Current Knowledge ◽  
Prognostic Significance ◽  
Good Prognosis ◽  
The Cancer Genome Atlas ◽  
Therapeutic Implications ◽  
Repair Deficiency ◽  
Cancer Genome Atlas

Endometrial cancer (EC) is the most common female malignancy in the world, it has traditionally been classified into two subgroups based on histopathological features, however this dualistic classification does not take into consideration subtypes such as high-grade endometrioid EC. Recently, work performed as part of The Cancer Genome Atlas study has focused on molecular genomic classification of EC, with four distinct molecular subtypes described: 1. POLE ultramutated, associated with a good prognosis; 2. Microsatellite instability (MSI) hypermutated; 3. Copy number low and microsatellite stable; 4. Copy number high, serous like, associated with a poor prognosis. The subgroup of patients with MSI is of particular interest for a number of reasons, including the use of tumour screening to identify patients with Lynch syndrome, the prognostic significance of MSI, and the potential therapeutic implications. This review will focus on the current knowledge in these areas and potential future directions.

Molecular testing in endometrial carcinoma – joint recommendation of Czech Oncological Society, Oncogynecological Section of the Czech Gynecological and Obstetrical Society, Society of Radiation Oncology, Biology and Physics, and the Society of Czech Pathologists

2021 ◽  
Vol 86 (4) ◽  
pp. 264-272
Author(s):  
Pavel Dundr ◽  
◽  
David Cibula ◽  
Martin Doležel ◽  
Pavel Fabián ◽  
...  
Keyword(s):  
Endometrial Carcinoma ◽  
European Society ◽  
Radiation Oncology ◽  
Molecular Classification ◽  
World Health ◽  
Molecular Testing ◽  
Therapeutic Implications ◽  
Health Organization ◽  
Endometrial Carcinomas

Summary: Molecular classification of endometrial carcinoma is becoming an important part of the dia gnostic process with direct therapeutic implications. Recent international guidelines, including the joint recommendation of the European Society of Gynaecological Oncology, the European Society for Radiotherapy and Oncology and the European Society of Pathology include the molecular classification into standard diagnostic algorithms. Molecular testing of endometrial carcinomas is also recommended in the latest (5th edition) of the World Health Organization classification of female genital tumors. Due to the need to implement these recommendations in practice, representatives of four professional societies of the Czech Medical Association of J. E. Purkyně (the Czech Oncological Society, the Oncogynecological Section of the Czech Gynecological and Obstetrical Society, the Society of Radiation Oncology, Biology and Physics, and the Society of Czech Pathologists) organized a meeting focused on this topic. Recommendation for molecular testing of endometrial carcinoma in routine dia gnostic practice in the Czech Republic.

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