- The emerging role of molecular pathology in directing the systemic treatment of endometrial cancerby Amy Jamieson on 2021-08-19
Following the discovery of the four molecular subtypes of endometrial cancer (EC) by The Cancer Genome Atlas (TCGA) in 2013, subsequent studies used surrogate markers to develop and validate a clinically relevant EC classification tool to recapitulate TCGA subtypes. Molecular classification combines focused sequencing (POLE) and immunohistochemistry (mismatch repair and p53 proteins) to assign patients with EC to one of four molecular subtypes: POLEmut, MMRd, p53abn and NSMP (no specific...
- Reply to Survival analysis and treatment effects in patients with endometrial cancer and POLE mutationsby Aline Talhouk on 2021-07-27
- Evaluation of treatment effects in patients with endometrial cancer and POLE mutations: An individual patient data meta-analysisby Jessica N McAlpine on 2021-04-01
CONCLUSIONS: Clinical outcomes for ECs with pathogenic POLE mutations are not associated with most traditional risk parameters, and patients do not appear to benefit from adjuvant therapy. The observed low rates of recurrence/progression and the high and sustained salvage rates raise the possibility of safely de-escalating treatment for these patients.
- p53abn Endometrial Cancer: understanding the most aggressive endometrial cancers in the era of molecular classificationby Amy Jamieson on 2021-02-16
Over the past decade, our understanding of endometrial cancer has changed dramatically from the two-tiered clinicopathologic classification system of type I and type II endometrial cancer through to the four distinct molecular subtypes identified by The Cancer Genome Atlas (TCGA) in 2013. In both systems there is a small subset of endometrial cancers (serous histotype/high numbers of somatic copy number abnormalities) that account for a disproportionately high percentage of endometrial cancer...
- Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancersby Dylan M Glubb on 2020-11-04
CONCLUSIONS: Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis.
- Whole-proteome analysis of mesonephric-derived cancers describes new potential biomarkersby Evan Gibbard on 2020-10-30
Mesonephric carcinomas (MEs) and female adnexal tumors of probable Wolffian origin (FATWO) are derived from embryologic remnants of Wolffian/mesonephric ducts. Mesonephric-like carcinomas (MLCs) show identical morphology to ME of the cervix but occur in the uterus and ovary without convincing mesonephric remnants. ME, MLC, and FATWO are challenging to diagnose due to their morphologic similarities to Müllerian/paramesonephric tumors, contributing to a lack of evidence-based and tumor-specific...
- Establishment and characterization of VOA1066 cells: An undifferentiated endometrial carcinoma cell lineby Yemin Wang on 2020-10-14
Dedifferentiated endometrial carcinoma (DDEC) is a rare but highly aggressive type of endometrial cancer, in which an undifferentiated carcinoma arises from a low-grade endometrioid endometrial carcinoma. The low-grade component is often eclipsed, likely due to an outgrowth of the undifferentiated component, and the tumor may appear as a pure undifferentiated endometrial carcinoma (UEC). We and others have recently identified inactivating mutations of SMARCA4, SMARCB1 or ARID1B, subunits of the...
- Molecular characterization of invasive and in situ squamous neoplasia of the vulva and implications for morphologic diagnosis and outcomeby Basile Tessier-Cloutier on 2020-08-15
Human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (VSCC) is an aggressive clinical entity. Current diagnostic guidelines for premalignant lesions are ambiguous, and their molecular profile and progression events are still unclear. We selected 75 samples, from 40 patients, including 33 VSCC, 8 verrucous carcinomas (VC), 13 differentiated-type vulvar intraepithelial neoplasia (dVIN), 11 suspicious for dVIN (?dVIN), 6 differentiated exophytic vulvar intraepithelial lesions...
- Endometrial Cancer Molecular Risk Stratification is Equally Prognostic for Endometrioid Ovarian Carcinomaby Pauline Krämer on 2020-08-02
CONCLUSIONS: EC-inspired molecular classification provides independent prognostic information in ENOC. Our findings support investigating molecular subtype-specific management recommendations for patients with ENOC; for example, subtypes may provide guidance when fertility-sparing treatment is desired. Similarities between ENOC and EC suggest that patients with ENOC may benefit from management strategies applied to EC and the opportunity to study those in umbrella trials.
- Fertility-sparing treatment in early endometrial cancer: current state and future strategiesby Andreas Obermair on 2020-07-22
Endometrial cancer (EC) is the fifth most common cancer in women worldwide. Global estimates show rising incidence rates in both developed and developing countries. Most women are diagnosed postmenopausal, but 14-25% of patients are premenopausal and 5% are under 40 years of age. Established risk factors include age and hyperestrogenic status associated with nulliparity, obesity, and metabolic syndrome. Standard treatment for EC, which involves total hysterectomy and bilateral...
- Single cell transcriptomes of normal endometrial derived organoids uncover novel cell type markers and cryptic differentiation of primary tumoursby Dawn R Cochrane on 2020-07-21
Endometrial carcinoma, the most common gynaecological cancer, develops from endometrial epithelium which is composed of secretory and ciliated cells. Pathologic classification is unreliable and there is a need for prognostic tools. We used single cell sequencing to study organoid model systems derived from normal endometrial endometrium to discover novel markers specific for endometrial ciliated or secretory cells. A marker of secretory cells (MPST) and several markers of ciliated cells (FAM92B,...
- FGFR2c Mesenchymal Isoform Expression Is Associated with Poor Prognosis and Further Refines Risk Stratification within Endometrial Cancer Molecular Subtypesby Asmerom T Sengal on 2020-05-17
CONCLUSIONS: FGFR2c expression appears an independent prognostic biomarker in patients with EEC and further discerns the outcomes within grade 3 tumors, ESMO high-risk groups, as well as within the MMRd and p53wt subtypes. FGFR2c inclusion into future molecular subtyping can further refine risk stratification of EEC.
- BRCA1 Promoter Methylation and Clinical Outcomes in Ovarian Cancer: An Individual Patient Data Meta-Analysisby Roshni D Kalachand on 2020-05-16
CONCLUSION: BRCA1-methylated OC displays similar clinicopathological features to BRCA1-mutated OC but is not associated with survival. Heterogeneity within BRCA1 methylation assays influences associations. Refining these assays may better identify cases with silenced BRCA1 function and improved patient outcomes.
- Arginine Depletion Therapy with ADI-PEG20 Limits Tumor Growth in Argininosuccinate Synthase-Deficient Ovarian Cancer, Including Small-Cell Carcinoma of the Ovary, Hypercalcemic Typeby Jennifer X Ji on 2020-05-16
CONCLUSIONS: Preclinical in vitro and in vivo studies identified ADI-PEG20 as a potential therapy for patients with rare ovarian cancers, including SCCOHT.
- Improving response to progestin treatment of low-grade endometrial cancerby Eva Baxter on 2020-05-09
OBJECTIVES: This review examines how response rates to progestin treatment of low-grade endometrial cancer can be improved. In addition to providing a brief overview of the pathogenesis of low-grade endometrial cancer, we discuss limitations in the current classification of endometrial cancer and how stratification may be refined using molecular markers to reproducibly identify 'low-risk' cancers which may represent the best candidates for progestin therapy. We also discuss constraints in...