High-grade Endometrial Carcinomas: Morphologic Spectrum and Molecular Classification

2021 ◽  
Author(s):  
Cunxian Zhang ◽  
Wenxin Zheng
Keyword(s):  
Molecular Classification ◽  
High Grade ◽  
Endometrial Carcinomas

scholarly journals Mismatch Repair Deficiency as a Predictive and Prognostic Biomarker in Molecularly Classified Endometrial Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3124
Author(s):  
Mikko Loukovaara ◽  
Annukka Pasanen ◽  
Ralf Bützow
Keyword(s):  
Risk Factors ◽  
Mismatch Repair ◽  
Molecular Classification ◽  
The Cancer Genome Atlas ◽  
Molecular Profile ◽  
New Therapeutic Approaches ◽  
Increased Risk ◽  
Mmr Deficiency ◽  
Endometrial Carcinomas ◽  
Risk Of Cancer

The aggressiveness of mismatch repair (MMR) deficient endometrial carcinomas was examined in a single institution retrospective study. Outcomes were similar for MMR proficient (n = 508) and deficient (n = 287) carcinomas, identified by immunohistochemistry. In accordance with molecular classification based on The Cancer Genome Atlas (TCGA), tumors with abnormal p53 staining or polymerase-ϵ exonuclease domain mutation were excluded from the MMR proficient subgroup, termed as “no specific molecular profile” (NSMP). Compared with NSMP (n = 218), MMR deficiency (n = 191) was associated with poor disease-specific survival (p = 0.001). MMR deficiency was associated with an increased risk of cancer-related death when controlling for confounders (hazard ratio 2.0). In the absence of established clinicopathologic risk factors, MMR deficiency was invariably associated with an increased risk of cancer-related death in univariable analyses (hazard ratios ≥ 2.0). In contrast, outcomes for MMR deficient and NSMP subgroups did not differ when risk factors were present. Lymphatic dissemination was more common (p = 0.008) and the proportion of pelvic relapses was higher (p = 0.029) in the MMR deficient subgroup. Our findings emphasize the need for improved triage to adjuvant therapy and new therapeutic approaches in MMR deficient endometrial carcinomas.

Prognostic impact of histological review of high-grade endometrial carcinomas in a large Danish cohort

2021 ◽  
Author(s):  
Marie Boennelycke ◽  
Elke E. M. Peters ◽  
Alicia Léon-Castillo ◽  
Vincent T. H. B. M. Smit ◽  
Tjalling Bosse ◽  
...  
Keyword(s):  
Prognostic Impact ◽  
High Grade ◽  
Danish Cohort ◽  
Endometrial Carcinomas

scholarly journals Differential Characteristics and Prognosis of PD-L1–Positive Endometrial Carcinomas: A Retrospective Chart Review

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1047
Author(s):  
Justin Z. Amarin ◽  
Razan Mansour ◽  
Sura Al-Ghnimat ◽  
Maysa Al-Hussaini
Keyword(s):  
Overall Survival ◽  
Tumor Cells ◽  
Chart Review ◽  
Prognostic Significance ◽  
Retrospective Chart Review ◽  
Cancer Center ◽  
High Grade ◽  
Endometrial Carcinomas

Women with endometrial carcinomas that express PD-L1 may respond better to immunotherapy. Our aim was to investigate the differential characteristics of PDL1–positive endometrial carcinomas and the prognostic significance of PDL1. We performed a retrospective chart review of 231 women with endometrial carcinomas who were managed at King Hussein Cancer Center (2007–2016) and performed immunohistochemistry for MLH1, PMS2, MSH2, MSH6, p53, and PD-L1. Overall, 89 cases (38.5%) were MMR-deficient. PD-L1 was expressed in 49 cases (21.2%) and its expression was significantly associated with MLH1/PMS2 deficiency (p = 0.044) but not MSH2/MSH6 deficiency (p = 0.59). p53 was mutant in 106 cases (46.5%), and its mutation was significantly associated with MMR proficiency (p < 0.001) but not PDL1 expression (p = 0.78). In women with endometrioid adenocarcinomas, PD-L1 expression was significantly associated with the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) grade (p = 0.008). Overall, PDL1 expression did not significantly predict overall survival in unadjusted or adjusted analyses (p = 0.92 and 0.54, respectively). In conclusion, tumors with MLH1/PMS2 loss and high-grade endometrioid adenocarcinomas were more likely to express PDL1 in tumor cells. Further research is required to investigate whether the presence of either characteristic signals a higher likelihood of a favorable response if immunotherapy is administered.

scholarly journals A Comparison of Death Domain-Associated Protein 6 in Different Endometrial Carcinomas Histotypes

2019 ◽  
Vol 14 ◽  
pp. 117727191986489
Author(s):  
Cao Jin ◽  
Sean Hacking ◽  
Miglena K Komforti ◽  
Mansoor Nasim
Keyword(s):  
Clear Cell ◽  
Point Mutations ◽  
Low Grade ◽  
Nuclear Staining ◽  
High Grade ◽  
Death Domain ◽  
Gynecology And Obstetrics ◽  
Grade 3 ◽  
Histologic Types ◽  
Endometrial Carcinomas

Background: Death domain-associated protein 6 (DAXX) is involved in regulating apoptosis via subcellular localization. The presence of DAXX point mutations correlates well with loss of nuclear expression on immunohistochemistry (IHC). In this study, we sought to determine (1) whether DAXX expression pattern is the same across different uterine carcinoma subtypes, and (2) which uterine carcinomas show loss of nuclear DAXX IHC. Design: We studied 65 uterine carcinomas of the following histologic types: 30 endometrioid (12 FIGO [The International Federation of Gynecology and Obstetrics] grade 1, 12 FIGO grade 2, and 6 FIGO grade 3), 8 serous, 14 clear cell, and 13 undifferentiated/dedifferentiated type (UEC/DDEC). Nuclear DAXX IHC was assessed in each tumor and was graded semi-quantitatively as follows: 0% to 50%, 50% to 75%, and greater than 75% of lesional cells react. Results: A total of 61% (25/41) of high-grade carcinomas (FIGO grade 3, serous, clear cell, and UEC/DDEC]) showed retained DAXX nuclear staining in >75% of lesional cells, compared with only 4.2% (1/24) of the low-grade carcinomas (FIGO grades 1 and 2) ( P = .0001), where DAXX expression was cytoplasmic. In addition, in the 11 DDEC cases, all the differentiated components showed loss of nuclear DAXX compared with the undifferentiated components which retained nuclear DAXX expression. Conclusions: We demonstrate that loss of nuclear DAXX is present in low-grade endometrial carcinomas and the differentiated components in UEC/DDEC, but not in high-grade ones, suggesting DAXX’s role in tumor progression and its potential as a therapeutic target in high-grade endometrial carcinomas.

High-Grade Endometrial Carcinomas

2019 ◽  
Vol 12 (2) ◽  
pp. 343-362 ◽  
Author(s):  
Joseph W. Carlson ◽  
Denis Nastic
Keyword(s):  
High Grade ◽  
Endometrial Carcinomas

scholarly journals Uterine Carcinomas in Tetrabromobisphenol A–exposed Wistar Han Rats Harbor IncreasedTp53Mutations and Mimic High-grade Type I Endometrial Carcinomas in Women

2015 ◽  
Vol 43 (8) ◽  
pp. 1103-1113 ◽  
Author(s):  
Janice B. Harvey ◽  
Tanasa S. Osborne ◽  
Hue-Hua L. Hong ◽  
Sachin Bhusari ◽  
Tai-Vu Ton ◽  
...  
Keyword(s):  
Tetrabromobisphenol A ◽  
Type I ◽  
High Grade ◽  
Endometrial Carcinomas

Targeting therapy based on preclinical analysis of clinical, molecular, and functional characteristics of individual high-grade serous ovarian cancers.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5073-5073
Author(s):  
Monique Topp ◽  
Lynne Hartley ◽  
Michele Cook ◽  
Dariush Etemadmoghadam ◽  
Laura Galleta ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Repair ◽  
Drug Response ◽  
Xenograft Model ◽  
Molecular Classification ◽  
Research Network ◽  
High Grade ◽  
Cancer Genome Atlas ◽  
Genome Atlas

5073 Background: Recent molecular exploration of high-grade epithelial ovarian cancer (OC) has revealed potential targets for novel therapy based on altered DNA repair function, deregulated pathways and recurrent amplifications (Cancer Genome Atlas Research Network. 2011. Nature 474). Improved pre-clinical models allowing analysis of specific molecular subsets of ovarian cancer are urgently required to test novel treatment strategies. Methods: We have generated a novel xenograft model of human high-grade serous OC (HG-SOC). Histologic, functional and molecular analysis of the novel xenograft cohort (at baseline and following xenotransplantation) allows stratification of individual HG-SOC for testing with appropriate targeted therapy. We perform functional analysis of in vitro Homologous Recombination (HR) DNA repair and drug response capabilities on fresh human HG-SOC immediately following surgical resection. Molecular classification (similar to Tothill [Clin Canc Res. 2008;14]); analysis of NHEJ pathway (Proc Natl Acad Sci. 2011;108) and other DNA repair genes (Proc Natl Acad Sci USA 2011;108) is performed. In vivo drug response is studied in murine xenografts. Results: Sixteen chemotherapy-naive potentially HG-SOC samples and associated clinical data have been collected. Functional evidence of DNA repair (HR) capability and response to DNA damaging agents will be presented, including IHC for markers of DNA damage (gH2AX), DNA repair (RAD51AP1) and apoptosis (capsase 3 cleavage). Molecular classification, DNA repair gene and DNA repair pathway analyses are underway. Twelve HG-SOC have been transplanted and 6 of the first 8 have successfully xenografted, with serial transplantation and phenotyping of xenograft derivatives underway. In vivo drug response will be presented. Conclusions: This xenograft model will enable us to address hypotheses generated by recent molecular analyses of human HG-SOC (Cancer Genome Atlas Research Network. 2011. Nature 474; Clin Canc Res. 2008;14). Clinical, functional and molecular annotation will allow pre-clinical drug testing based on the plausible hypothesis approach.

scholarly journals Molecular classification of high grade endometrioid and clear cell ovarian cancer using TCGA gene expression signatures

2016 ◽  
Vol 141 (1) ◽  
pp. 95-100 ◽  
Author(s):  
Boris Winterhoff ◽  
Habib Hamidi ◽  
Chen Wang ◽  
Kimberly R. Kalli ◽  
Brooke L. Fridley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Clear Cell ◽  
Molecular Classification ◽  
High Grade ◽  
Gene Expression Signatures
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