Related Experiment Video
Updated: Jan 21, 2026
Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression
Published on: February 3, 2023
MMR deficient undifferentiated/dedifferentiated endometrial carcinomas showing significant programmed death ligand-1
Sean Hacking1, Cao Jin1, Miglena Komforti1
1Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Northwell, New York, United States of America.
Background:
Uterine undifferentiated (UEAC)/dedifferentiated (DEAC) carcinomas are rare malignant neoplasms. They appear to pursue an aggressive clinical course with an advanced stage at presentation. Recently, it was discovered that the use of immunotherapeutic drugs targeting programmed cell death protein 1 (PD1)/programmed death ligand-1 (PD-L1) was associated with improved survival in several types of cancer (especially in patients with mismatch-repair (MMR) deficient patients). Whether these findings can be applied to UEAC/DEAC remains a question. Herein, the aim of this study is to evaluate the expression of PD-L1/PD-1 in UEAC/DEAC and its relationship to MMR status. This could offer useful therapeutic information.
Design:
Review of endometrial carcinoma (EC) diagnosed over the period of 2011 to 2017 in our institution identified 14 UEAC/DEAC cases (n=14). All cases had immunohistochemistry performed for MMR (MLH1, PMS2, MSH2 and MSH6), PD-L1 and PD-1. The protein expression was examined and in DEAC cases both the undifferentiated component and the low grade component were recorded separately. The expression of PD-L1 and PD-1 was scored in both the tumor and the peritumoral lymphocyte infiltration.
Results:
Overall variable degrees of tumoral or immune stromal PD-L1 staining (from 1% to 5%), was present in 50.0% (7/14) of UC/DEACs. Seven cases (50%) were PD-1 positive (immune stromal). Five cases (35.7%) showed co-expression of PD-1 and PD-L1 (Figure 1). Worth noting is that PD-1 staining was exclusively present in peritumoral immune cells. Following this the 14 cases were further divided into MMR deficient and MMR proficient groups (Table 1). A total of 8 cases had MMR deficiency (57.1%). There was a statistically significant association for PD-L1 positivity in the MMR deficiency group (p=0.05). However there was no statistically significant differences regarding PD-1 positivity between MMR groups.
Conclusions:
PD-L1 and PD-1 were expressed in majority of MMR-deficient UEAC /DEAC cases. PD-L1 was not expressed in MMR-proficient carcinomas. These findings might help support potential immunotherapy trials in MMR-deficient UEAC /DEAC.
Related Concept Videos
02:51Metal-Ligand Bonds
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
02:40Ligand Binding Sites
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
00:49Ligand Binding and Linkage
02:58Cell Potential and Free Energy
Thermodynamics is the branch of physics dealing with the relationship between heat and other forms of energy. In an electrochemical cell, chemical energy is converted into electrical energy.
Thus, a link can be predicted between cell potential, free energy change, and the equilibrium constant for the reaction. Cell potential can also be measured as the oxidant or the reducing strength, and similar acid-base strength measures are reflected in equilibrium...
01:13Therapeutic Index
03:02Standard Electrode Potentials