J Gynecol Oncol.  2017 Nov;28(6):e77. 10.3802/jgo.2017.28.e77.

Prognostic value of programmed death-ligand 1 (PD-L1) expression in ovarian clear cell carcinoma

• Zhu J
• Wen H
• Bi R
• Wu Y
• Wu X

• KMID: 2413203
• DOI: http://doi.org/10.3802/jgo.2017.28.e77

Abstract

OBJECTIVE
Programmed death-ligand 1 (PD-L1) was expressed in various tumors and antibodies targeting its receptor programmed cell death-1 (PD-1) are emerging cancer therapeutics. This study was designed to evaluate the expression of PD-L1 and its correlation with clinicopathologic features and clinical outcomes in ovarian clear cell carcinoma (OCCC).
METHODS
The PD-L1 expression was measured by tissue-microarray-based immunohistochemistry from 122 eligible patients diagnosed with OCCC. The associations of clinicopathologic features with progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method and multivariate analysis was further performed by Cox regression model.
RESULTS
Overall, high PD-L1 expression (PD-L1(high)) was observed in 44.7% (55/123) of OCCC patients, and was strongly associated with advanced stages (p=0.020), positive ascitic fluid (p=0.016), platinum-resistant (PR) disease (p=0.045), and recurrence (p=0.038). Moreover, patients with PD-L1(high) were associated with poorer OS (hazard ratio [HR]=2.877; p=0.001) and PFS (HR=1.843; p=0.021) than those with low PD-L1 expression (PD-L1(low)). In subgroup analysis, PD-L1(high) patients experienced a poorer PFS (HR=1.926; p=0.044) and OS (HR=2.492; p=0.021) than PD-L1(low) cases among advanced stages (III-IV), but this difference was not observed in stage I-II patients. Meanwhile, PD-L1(high) was associated with poorer prognosis than PD-L1(low) in PR patients (OS, HR=2.253; p=0.037; PFS, HR=1.448; p=0.233). Multivariate analysis revealed that PD-L1(high) and advanced stages (III-IV) were adverse independent prognosticators for both PFS (HR(PD-L1)=2.0; p(PD-L1)=0.038; HR(stage)=10.2; p(stage)<0.001) and OS (HR(PD-L1)=3.0; p(PD-L1)=0.011; HR(stage)=14.3; p(stage)<0.001).
CONCLUSION
PD-L1(high) might serve as a risk factor for PFS and OS in patients with OCCC. It is possible that immunotherapy targeting PD-L1 pathway could be used in OCCC.

Keyword

Ovarian Neoplasms; Adenocarcinoma, Clear Cell; Antigens, CD274; Prognosis

MeSH Terms

Adenocarcinoma, Clear Cell/*metabolism
Adult
Aged
Aged, 80 and over
B7-H1 Antigen/*metabolism
Disease-Free Survival
Female
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Middle Aged
Multivariate Analysis
Ovarian Neoplasms/*metabolism
Prognosis
Proportional Hazards Models
Survival Rate
Tissue Array Analysis
Young Adult
B7-H1 Antigen

Figure

• 

  Fig. 1. The overview of staining intensities of the tissue array is shown (3+. 2+, 1+, and 0+), with an example each (A-D) for a membranous and/or for a cytoplasmic staining pattern.

• 

  Fig. 2. Immunohistochemical staining for PD-L1 in OCCC tumor tissues. The staining intensities are shown (0+, 1+, 2+, 3+), with an example each (A-D) for a membranous and/or a cytoplasmic staining pattern. The placenta tissue (E) is used as a positive control for PD-L1 expression. The total number of each staining intensity are shown in (F). OCCC, ovarian clear cell carcinoma; PD-L1, programmed death-ligand 1.

• 

  Fig. 3. (A, B) PFS and OS curves in patients with OCCC. (C) Patients with PD-L1 high (blue dotted line) showed significantly worse PFS compared with those with low expression (yellow solid line). (D) Patients with PD-L1 low (yellow solid line) presented a better survival outcome than those with PD-L1 high (blue dotted line). OCCC, ovarian clear cell carcinoma; OS, overall survival; PD-L1, programmed death-ligand 1; PD-L1 high, high PD-L1 expression; PD-L1 low, low PD-L1 expression; PFS, progression-free survival.

• 

  Fig. 4. PFS and OS curves stratified by FIGO stage between high and low PD-L1 expression (yellow solid lines, PD-L1 low; blue dotted lines, PD-L1 high, respectively). (A) OS curves between high and PD-L1 low in FIGO stage I/II cases. (B) PFS curves between high and PD-L1 low in FIGO stage I/II cases. (C) OS curves between high and PD-L1 low in stage III/IV cases. (D) PFS curves between high and PD-L1 low in stage III/IV cases. Patients with PD-L1 high revealed a worse OS and PFS compared with those with PD-L1 low in stage III/IV cases, with significant differences observed. FIGO, International Federation of Gynecology and Obstetrics; OCCC, ovarian clear cell carcinoma; OS, overall survival; PD-L1, programmed death-ligand 1; PD-L1 high, high PD-L1 expression; PD-L1 low, low PD-L1 expression; PFS, progression-free survival.

• 

  Fig. 5. PFS and OS curves stratified by the sensitivity to chemotherapy between high and low PD-L1 expression (yellow solid lines, PD-L1 low; blue dotted lines, PD-L1 high, respectively). (A) OS curves between high and PD-L1 low in PS cases. (B) PFS curves between high and PD-L1 low in PS cases. (C) OS curves between high and PD-L1 low in PR cases. (D) PFS curves between high and PD-L1 low in PR cases. Patients with PD-L1 high revealed a worse OS and PFS compared with those with PD-L1 low in PR cases, with significant differences observed. OS, overall survival; PD-L1, programmed death-ligand 1; PD-L1 high, high PD-L1 expression; PD-L1 low, low PD-L1 expression; PFS, progression-free survival; PR, platinum-resistant; PS, platinum-sensitive.

Reference

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