Correlation of PD-L1 expression with immunohistochemically determined molecular profile in endometrial carcinomas

Kır, Gözde; Soylemez, Tuce; Olgun, Zeynep Cagla; Aydın, Abdullah; McCluggage, W. Glenn

doi:10.1007/s00428-020-02867-9

Cited by 21 publications

(24 citation statements)

References 52 publications

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“…Some authors have shown the same results [12,15]. Other authors have shown no association [17][18][19]. In addition, Sungu et al showed that the FIGO grade of endometrioid adenocarcinomas is associated with PD-L1 expression in immune cells but not tumor cells [20].…”

Section: Discussionmentioning

confidence: 92%

Differential Characteristics and Prognosis of PD-L1–Positive Endometrial Carcinomas: A Retrospective Chart Review

Amarin

Mansour

Al-Ghnimat

et al. 2021

Life

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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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Section: Discussionmentioning

confidence: 92%

Differential Characteristics and Prognosis of PD-L1–Positive Endometrial Carcinomas: A Retrospective Chart Review

Amarin

Mansour

Al-Ghnimat

et al. 2021

Life

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“…A total of 12 studies, with 3023 EC cases, were finally included in this review [ 17 , 18 , 19 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. All studies used the data from immunohistochemistry (IHC) for positive PD-L1 expression.…”

Section: Resultsmentioning

confidence: 99%

“…The earliest study was published in May 2016 by Mo and colleagues [ 19 ], and the most recent study was published in February 2021 by Siraj and colleagues [ 18 ]. The most extensive study was conducted by Pasanen et al (2019) [ 27 ] with 842 patients, and the smallest study was carried out by Chew et al (2020) [ 31 ] and Kir et al (2020) [ 28 ], which included 59 patients each. All of the included studies and variables of interest associated with PD-L1 expression in EC are summarised in Table 2 .…”

Section: Resultsmentioning

confidence: 99%

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PD-L1 Expression in Endometrial Cancer and Its Association with Clinicopathological Features: A Systematic Review and Meta-Analysis

Yusof

Chew

Kampan

et al. 2022

Cancers

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Endometrial cancer (EC) is one of the most common malignancies of the female genital tract and its current treatment mainly relies on surgical removal of the tumour bulk, followed by adjuvant radiotherapy with or without chemotherapy/hormonal therapy. However, the outcomes of these approaches are often unsatisfactory and are associated with severe toxicity and a higher recurrence rate of the disease. Thus, more clinical research exploring novel medical intervention is needed. Involvement of the immune pathway in cancer has become important and the finding of a high positive expression of programmed cell death-ligand 1 (PD-L1) in EC may offer a better targeted therapeutic approach. Numerous studies on the PD-L1 role in EC have been conducted, but the results remained inconclusive. Hence, this systematic review was conducted to provide an update and robust analysis in order to determine the pooled prevalence of PD-L1 expression in EC and evaluate its association with clinicopathological features in different focuses of tumour cells (TC) and immune cells (IC). A comprehensive literature search was conducted using the PubMed, Web of Science, and Scopus databases. Twelve articles between 2016 and 2021 with 3023 EC cases met the inclusion criteria. The effect of PD-L1 expression on the outcome parameters was estimated by the odds ratios (ORs) with 95% confidence intervals (CIs) for each study. The pooled prevalence of PD-L1 was 34.26% and 51.39% in the tumour cell and immune cell, respectively, among women with EC. The PD-L1 expression was significantly associated with Stage III/IV disease (in both TC and IC) and correlated to the presence of lympho-vascular invasion in IC. However, the PD-L1 expression in TC was not associated with the age groups, histology types, myometrial invasion, and lympho-vascular invasion. In IC, PD-L1 expression was not associated with age group, histology type, and myometrial invasion. The meta-analysis survival outcomes of PD-L1 high expression had a significant association with worse OS in IC but not in TC.

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“…Adenosarcoma and endometrial adenocarcinoma are considered separate diseases, although endometrioid carcinoma mixed with clonally related adenosarcoma is reported [ 4 ]. Lenvatinib/pembrolizumab is active in metastatic or unresectable endometrial adenocarcinoma, despite low prevalence of PD-L1 expression [ 5 ] and regardless of MMR protein status [ 6 ]. Although our patient’s tumor did not have any adenocarcinoma component, given the lack of standard therapeutic options and the absence of any suitable clinical trial in our institution, this regimen was offered to her on the basis of the known sensitivity of various sarcomas to antiangiogenic tyrosine kinase inhibitors [ 7 , 8 ] and of the synergy observed between the latter and immune checkpoint inhibitors [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical Benefit from Lenvatinib and Pembrolizumab Observed in Mullerian Adenosarcoma: A Case Report

2021

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Correlation of PD-L1 expression with immunohistochemically determined molecular profile in endometrial carcinomas

Cited by 21 publications

References 52 publications

Differential Characteristics and Prognosis of PD-L1–Positive Endometrial Carcinomas: A Retrospective Chart Review

Differential Characteristics and Prognosis of PD-L1–Positive Endometrial Carcinomas: A Retrospective Chart Review

PD-L1 Expression in Endometrial Cancer and Its Association with Clinicopathological Features: A Systematic Review and Meta-Analysis

Clinical Benefit from Lenvatinib and Pembrolizumab Observed in Mullerian Adenosarcoma: A Case Report

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