en en en id ca en en en en en en en en en en en en en en en en en en en en en fr en de en en en en en en en en en en en en en en ceb en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en de en en en en en en en en en en en en en en en jbo en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en fa en en en en en en en en en en en en en en en en en en en en en en en en
Immune checkpoint expression, microsatellite instability, and mutational burden: Identifying immune biomarker phenotypes in uterine cancer | Caris Life Sciences
Nathaniel L Jones, Joanne Xiu, Rodney P Rocconi, Thomas J Herzog, Ira S Winer
Increasing grade of endometrioid endometrial cancer (EEC) is associated with aggressive behavior and poor prognosis. The traditional classification system is limited in its ability to guide treatment planning and prognostication. We identify distinct immune biomarker phenotypes using known markers of immunogenicity to identify patients who may benefit from immune therapy (IT).
621 tumors were analyzed by multiplatform profiling. NextGen sequencing was performed on 592 genes. Tumor mutational burden (TMB) was defined as high (H) ≥10mutations/megabase. Microsatellite Instability (MSI) by NGS was ≥46 loci. PD-L1 positivity was ≥2+, >5% by IHC. Chi-square tests were used.
Overall, MSI-H was found in 33% of EECs, most frequent in grade 3 (G3), followed by grade 2 (G2) and grade 1 (G1) tumors (G3: 37%, G2: 32%, G1: 22%, p = 0.007). TMB-H was identified in 25% of EECs. TMB-H was most common in G3, followed by G2 and G1 tumors (G3: 34%, G2: 23%, G1: 13%, p = 0.006). Overall, PD-L1 expression was found in 5.5% of EECs. G3 EECs had the most frequent PD-L1 expression, followed by G2 and G1 tumors (G3: 12%, G2: 3.0%, G1: 0.9%, p < 0.0001). We identified POLE mutations in 4.5% (28/618). All POLE mutated tumors harbored TMB-H phenotypes but MSI-H and PD-L1 were only present in 10.7% and 14.8% of tumors respectively, suggesting upregulation of T-cell immune response in only a fraction of POLE mutated EECs. Triple negative (TN) biomarker phenotype (ER-/PR-/Her2-) was evaluated as a potential surrogate marker of tumor immunogenicity. We identified TN phenotype in 4% of G1 EEC compared with 9% in G2 and 33% in G3, suggesting loss of hormone expression and possible greater immunogenicity with increasing tumor grade.
High grade tumors appear to be more immunogenic than low grade tumors and may preferentially benefit from IT.
Biomarkers; Checkpoint inhibitors; Endometrial; Immune.
Caris Molecular Tumor Board
Laboratory Accreditations & Licenses
Privacy & Website Policies
Annual Notice to Physicians
© 2022 Caris Life Sciences. All rights reserved.
We use cookies on our website to give you the most relevant experience by remembering your preferences and repeat visits. By clicking “Accept,” you consent to the use of all cookies.
Do not sell my personal information.
This website uses cookies to improve your experience while you navigate through the website. Out of these, the cookies that are categorized as necessary are stored on your browser as they are essential for the working of basic functionalities of the website. We also use third-party cookies that help us analyze and understand how you use this website. These cookies will be stored in your browser only with your consent. You also have the option to opt-out of these cookies. But opting out of some of these cookies may affect your browsing experience.
Necessary cookies are absolutely essential for the website to function properly. These cookies ensure basic functionalities and security features of the website, anonymously.
This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Analytics".
The cookie is set by GDPR cookie consent to record the user consent for the cookies in the category "Functional".
This cookie is set by GDPR Cookie Consent plugin. The cookies is used to store the user consent for the cookies in the category "Necessary".
This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Other.
This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Performance".
The cookie is set by the GDPR Cookie Consent plugin and is used to store whether or not user has consented to the use of cookies. It does not store any personal data.
Functional cookies help to perform certain functionalities like sharing the content of the website on social media platforms, collect feedbacks, and other third-party features.
Performance cookies are used to understand and analyze the key performance indexes of the website which helps in delivering a better user experience for the visitors.
Analytical cookies are used to understand how visitors interact with the website. These cookies help provide information on metrics the number of visitors, bounce rate, traffic source, etc.
Advertisement cookies are used to provide visitors with relevant ads and marketing campaigns. These cookies track visitors across websites and collect information to provide customized ads.
Other uncategorized cookies are those that are being analyzed and have not been classified into a category as yet.