AI Article Synopsis
- There is a significant challenge in diagnosing ovarian high-grade endometrioid carcinoma (HGEC) and high-grade serous carcinoma (HGSC) due to their similar histopathological features, leading to variability among observers.
- A study analyzed a variety of ovarian cancer samples using advanced sequencing and clustering techniques, identifying four distinct tumor groups with different characteristics and survival outcomes.
- The findings suggest that a specific subset of tumors, termed "HGEC-type," shows favorable prognosis and endometrial differentiation, which may often be misclassified as HGSCs, indicating a need for improved diagnostic strategies.
Article Abstract
Background: Considerable interobserver variability exists in diagnosis of ovarian high-grade endometrioid carcinoma (HGEC) and high-grade serous carcinoma (HGSC) due to histopathological similarities. While homologous recombination deficiency (HRD) correlates with drug sensitivity in HGSC, the molecular features of HGEC are unclear.
Methods: Fresh-frozen samples from 15 ovarian HGECs and 274 ovarian HGSCs in the JGOG-TR2 cohort were submitted to targeted DNA sequencing, RNA sequencing, DNA methylation array, and SNP array. We additionally analyzed 555 ovarian HGSCs from TCGA-OV and 287 endometrial high-grade carcinomas from TCGA-UCEC.
Results: Unsupervised clustering using copy number signatures identified four distinct tumor groups (C1, C2, C3 and C4). C1 (n = 41) showed CCNE1 amplification and poor survival. C2 (n = 160) and C3 (n = 59) showed high BRCA1/2 alteration frequency with low and moderate ploidy, respectively. C4 (n = 22) was characterized by favorable outcome, higher HGEC proportion, no BRCA1/2 alteration or CCNE1 amplification, and low levels of HRD score, ploidy, intra-tumoral heterogeneity, cell proliferation rate, and WT1 gene expression. Notably, C4 exhibited a normal endometrium-like DNA methylation profile, thus, defined as "HGEC-type" tumors, which were also identified in TCGA-OV and TCGA-UCEC.
Conclusions: Ovarian "HGEC-type" tumors present a non-HRD status, favorable prognosis, and endometrial differentiation, possibly constituting a subset of clinically diagnosed HGSCs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11473812 | PMC |
| http://dx.doi.org/10.1038/s41416-024-02837-x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Epidermal growth factor receptor ligands enriched in follicular fluid exosomes promote oncogenesis of fallopian tube epithelial cells.
Cancer Cell Int
December 2024
Center for Prevention and Therapy of Gynecological Cancers, Department of Research, Hualien, 970, Taiwan, ROC.
Article Synopsis
- Incessant ovulation contributes to ovarian high-grade serous carcinomas (HGSC), which primarily arise from the fallopian tube epithelium (FTE), and receptor tyrosine kinase (RTK) ligands play a key role in this process.
- A study investigated follicular fluid exosomes from women undergoing in vitro fertilization to identify RTK ligands and their impact on FTE cells, using various RTK inhibitors.
- The findings revealed that FF exosomes were rich in transformative abilities and essential EGFR ligands, promoting cell growth and migration, indicating their significant contribution to HGSC development.
NSC-3852 synergistically enhances the cytotoxicity of olaparib in oral squamous cell carcinoma.
Biochem Biophys Res Commun
December 2024
Department of Pharmacology, Faculty of Dentistry, Osaka Dental University, 8-1 Kuzuhahanazono-cho, Hirakata, Osaka 573-1121, Japan. Electronic address:
The PARP inhibitor olaparib is an anti-cancer agent based on synthetic lethality that targets poly (ADP-ribose) polymerases. It is used as a therapeutic agent for breast, ovarian, pancreatic, and prostate cancers carrying BRCA1/2 mutations that cause deficiency in homologous recombination. In recent years, acquired resistance to PARP inhibitors has become a clinical problem in PARP inhibitor-treated patients.
View Article and Find Full Text PDFActionable mutations in early-stage ovarian cancer according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT): a descriptive analysis on a large prospective cohort.
ESMO Open
December 2024
Unit of Oncological Gynecology, Women's Children's and Public Health Department, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy. Electronic address: https://twitter.com/CamillaNero.
Background: According to the European Society for Clinical Oncology (ESMO) guidelines, the therapeutic algorithm for early-stage epithelial ovarian carcinoma (EOC) is primarily based on grading and histotype. Adjuvant chemotherapy is usually recommended for high-grade tumors and for the International Federation of Gynecology and Obstetrics (FIGO) stage IB-IC; however, overtreatment remains a concern. Conversely, patients truly at higher risk of recurrence currently lack access to additional therapeutic strategies.
View Article and Find Full Text PDFMultimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma.
Cancer Discov
December 2024
Brigham and Women's Hospital, Boston, MA, United States.
High-Grade Serous Ovarian Cancer (HGSOC) originates from fallopian tube (FT) precursors. However, the molecular changes that occur as precancerous lesions progress to HGSOC are not well understood. To address this, we integrated high-plex imaging and spatial transcriptomics to analyze human tissue samples at different stages of HGSOC development, including p53 signatures, serous tubal intraepithelial carcinomas (STIC), and invasive HGSOC.
View Article and Find Full Text PDFIntegrative multi-omics and machine learning approach reveals tumor microenvironment-associated prognostic biomarkers in ovarian cancer.
Transl Cancer Res
November 2024
Department of Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China.
Background: Ovarian cancer (OC) is a globally prevalent malignancy with significant morbidity and mortality, yet its heterogeneity poses challenges in treatment and prognosis. Recognizing the crucial role of the tumor microenvironment (TME) in OC progression, this study leverages integrative multi-omics and machine learning to uncover TME-associated prognostic biomarkers, paving the way for more personalized therapeutic interventions.
Methods: Employing a rigorous multi-omics approach, this study analyzed single-cell RNA sequencing (scRNA-seq) data from OC and normal tissue samples, including high-grade serous OC (HGSOC) from the Gene Expression Omnibus (GEO: GSE184880) and The Cancer Genome Atlas (TCGA) OC cohort, utilizing the Seurat package to annotate 700 TME-related genes.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!