Dedifferentiated Endometrial Carcinoma Could be A Target for Immune Checkpoint Inhibitors (Anti PD-1/PD-L1 Antibodies).
Int J Mol Sci
; 20(15)2019 Jul 31.
Article
en En
| MEDLINE
| ID: mdl-31370215
ABSTRACT
Dedifferentiated endometrial carcinoma (DDEC) is defined as an undifferentiated carcinoma admixed with differentiated endometrioid carcinoma (Grade 1 or 2). It has poor prognosis compared with Grade 3 endometrioid adenocarcinoma and is often associated with the loss of mismatch repair (MMR) proteins, which is seen in microsatellite instability (MSI)-type endometrial cancer. Recent studies have shown that the effectiveness of immune checkpoint inhibitor therapy is related to MMR deficiency; therefore, we analyzed the immunophenotype (MMR deficient and expression of PD-L1) of 17 DDEC cases. In the undifferentiated component, nine cases (53%) were deficient in MMR proteins and nine cases (53%) expressed PD-L1. PD-L1 expression was significantly associated with MMR deficiency (p = 0.026). In addition, the presence of tumor-infiltrating lymphocytes (CD8+) was significantly associated with MMR deficiency (p = 0.026). In contrast, none of the cases showed PD-L1 expression in the well-differentiated component. Our results show that DDEC could be a target for immune checkpoint inhibitors (anti PD-L1/PD-1 antibodies), especially in the undifferentiated component. As a treatment strategy for DDEC, conventional paclitaxel plus carboplatin and cisplatin plus doxorubicin therapies are effective for those with the well-differentiated component. However, by using immune checkpoint inhibitors in combination with other conventional treatments, it may be possible to control the undifferentiated component and improve prognosis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carcinoma
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Neoplasias Endometriales
/
Carcinoma Endometrioide
/
Anticuerpos Neutralizantes
/
Antineoplásicos Inmunológicos
Tipo de estudio:
Prognostic_studies
Límite:
Aged
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Int J Mol Sci
Año:
2019
Tipo del documento:
Article
País de afiliación:
Japón