Dataset Information

Stratification of ovarian tumor pathology by expression of programmed cell death-1 (PD-1) and PD-ligand- 1 (PD-L1) in ovarian cancer.

ABSTRACT:

Background

Ovarian cancer is the major cause of death among gynecologic cancers with 75% of patients diagnosed with advanced disease, and only 20% of these patients having a survival duration of five years. Treatments blocking immune checkpoint molecules, programmed cell death (PD-1) or its ligand PD-ligand- I (PD-L1) have produced a beneficial and prolonged effect in a subgroup of these patients. However, there is debate in the literature concerning the prognostic value of the expression of these molecules in tumors, with immunotherapy responsiveness, and survival. We evaluated the immune landscape of the ovarian tumor microenvironment of patients, by measuring the impact of the expression of tumor PD-1, PD-L1 and infiltrating lymphocytes on stage and grade of tumors and survival, in a cohort of 55 patients with gynecologic malignancies. Most patients under study were diagnosed with advanced disease ovarian cancer.

Results

Our studies revealed that a low density of PD-1 and of PD-L1 expressing cells in tumor tissue were significantly associated with advanced disease (P?=?0.028 and P?=?0.033, respectively). Moreover, PD-L1 was expressed significantly more often in high grade tumors (41.5%) than in low grade tumors of patients (7.7%) (P?=?0.040). The presence of CD3 or of FoxP3 infiltrating cells with PD-L1 in patient tumors did not impact the significance of the association of PD-L1 with high grade tumors (P?=?0.040), and our analyses did not show an association between the presence of PD-1 or PD-L1 and survival.

Conclusions

We conclude that a subgroup of advanced disease ovarian cancer patients with high grade tumors, expressing PD-L1, may be prime candidates for immunotherapy targeting PD-1 signaling.

SUBMITTER: Drakes ML

PROVIDER: S-EPMC5975524 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Publications

Stratification of ovarian tumor pathology by expression of programmed cell death-1 (PD-1) and PD-ligand- 1 (PD-L1) in ovarian cancer.

Drakes Maureen L ML Mehrotra Swati S Aldulescu Monica M Potkul Ronald K RK Liu Yueying Y Grisoli Anne A Joyce Cara C O'Brien Timothy E TE Stack M Sharon MS Stiff Patrick J PJ

Journal of ovarian research 20180530 1

<h4>Background</h4>Ovarian cancer is the major cause of death among gynecologic cancers with 75% of patients diagnosed with advanced disease, and only 20% of these patients having a survival duration of five years. Treatments blocking immune checkpoint molecules, programmed cell death (PD-1) or its ligand PD-ligand- I (PD-L1) have produced a beneficial and prolonged effect in a subgroup of these patients. However, there is debate in the literature concerning the prognostic value of the expressio ...[more]

PMID: 29843813

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Project description:Objectives: Thymic epithelial tumors (TETs) are rare malignant tumors that exhibit heterogeneous histology and clinical behavior. As immune check point inhibitors, drugs targeting anti-programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) have shown remarkable results against many cancers; thus, the importance of PD-1/PD-L1 immunohistochemistry as a predictive or prognostic biomarker has grown. However, limited data on PD-L1 and PD-1 expression in TETs have been reported; moreover, these results have been variable. Here, we examined the expression of PD-1/PD-L1 proteins in TETs and analyzed the clinicopathologic significance of this expression. Patients and Methods: A tissue microarray was constructed using 368 samples of TETs, each in triplicate. Immunohistochemistry for PD-L1 (SP263 assay) and PD-1 in TETs and CD8 in thymic carcinoma (TC) was performed; next, correlations with clinicopathologic characteristics were analyzed. PD-L1high was designated as ?50% of tumor proportion score; PD-1high and CD8high were defined as ?5% and 1% of tumoral immune cells, respectively. Results: The cohort consisted of 308 patients with thymomas and 60 patients with TC. PD-L1 positivity was identified in 90.6% (328/362, ?1%) of TETs, PD-1 expression of intra-/peritumoral T cells was identified in 53.6% (194/362) of TETs and CD8 positivity was identified in 11% (7/60, ?1%) of TC. Of the 362 patients, 141 (39.0%) exhibited high PD-L1 expression (PD-L1high). The PD-L1high thymoma group was correlated with high Masaoka-Koga stage (p < 0.001), type B3 histology (p < 0.001), and myasthenia gravis (p < 0.001). This group exhibited poor overall survival (OS, p = 0.003, log-rank) and worse disease-free survival (DFS, p = 0.042, log-rank). No survival differences were detected between PD-L1high and PD-L1low groups in TC. Additionally, there was no correlation between PD-1 expression and survival in patients with TETs. Multivariate analysis revealed that PD-L1high expression was an independent poor prognostic factor (p = 0.047, HR 2.087, 95% CI, 1.009-4.318) in thymomas. Conclusions: To our knowledge, this is the largest study on TETs published in English literature. This study provides useful information regarding the prognosis of and potential therapeutic options for patients with TETs.

Dataset Information

Stratification of ovarian tumor pathology by expression of programmed cell death-1 (PD-1) and PD-ligand- 1 (PD-L1) in ovarian cancer.

Background

Results

Conclusions

Publications

Stratification of ovarian tumor pathology by expression of programmed cell death-1 (PD-1) and PD-ligand- 1 (PD-L1) in ovarian cancer.

Similar Datasets

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