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- Title
Dedifferentiated Endometrial Carcinoma Could be A Target for Immune Checkpoint Inhibitors (Anti PD-1/PD-L1 Antibodies).
- Authors
Ono, Ruriko; Nakayama, Kentaro; Nakamura, Kohei; Yamashita, Hitomi; Ishibashi, Tomoka; Ishikawa, Masako; Minamoto, Toshiko; Razia, Sultana; Ishikawa, Noriyoshi; Otsuki, Yoshiro; Nakayama, Satoru; Onuma, Hideyuki; Kurioka, Hiroko; Kyo, Satoru
- 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.
- Subjects
PROGRAMMED cell death 1 receptors; CARCINOMA; IMMUNOGLOBULINS; ENDOMETRIAL cancer; PACLITAXEL
- Publication
International Journal of Molecular Sciences, 2019, Vol 20, Issue 15, p3744
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms20153744