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.

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

Biomarker Insights ◽

10.1177/1177271919864892 ◽

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.

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