PD-L1 expression in Xp11.2 translocation renal cell carcinoma: Indicator of tumor aggressiveness

Kun Chang,Dingwei Ye,Hualei Gan,Guohai Shi,Bo Dai,Hailiang Zhang,Yao Zhu,Jian-Yuan Zhao,Yuanyuan Qu,Yiping Zhu,Yijun Shen

doi:10.1038/s41598-017-02005-7

Abstract

Programmed death ligand-1 (PD-L1), a promising antitumor target, has proven clinical value against many malignancies. However, the PD-L1 content of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and its correlation with clinical outcomes remain unclear. This study aimed to investigate PD-L1 expression in Xp11.2 RCC and to assess its prognostic value. Formalin-fixed paraffin-embedded specimens from 36 adult patients that were histologically confirmed (by fluorescence in situ hybridization) were subjected to immunohistochemical analysis. Of the 36 Xp11.2 RCC patients, 9 (25.0%) had tumors with positive PD-L1 expression and 27 (75.0%) had tumors with negative PD-L1 expression. Positive PD-L1 expression correlated with advanced tumor stage (P = 0.001), regional lymph node metastasis (P < 0.001), and distant metastasis (P < 0.001). A multivariate analysis identified positive PD-L1 expression was an independent adverse prognostic factor for both progression free survival (hazard ratio: 3.7, P = 0.018) and overall survival (hazard ratio: 4.5, P = 0.034). The median PFS and OS for the whole cohort were 13.0 months (95% confidence interval [CI], 9.4–16.6 months) and 36.0 months (95% CI, 23.9–48.1 months), respectively. Our findings suggest that positive PD-L1 expression is indicative of worse clinical outcome in Xp11.2 RCC. Further studies are needed to explore the potential efficacy of targeting PD-L1 in Xp11.2 RCC.

Highlights

Programmed death ligand-1 (PD-L1), a promising antitumor target, has proven clinical value against many malignancies
Thompson et al were among the first to identify the clinical significance of PD-L1 expression in clear cell Renal cell carcinoma (RCC) patients using immunohistochemical methods[18,19,20]
These authors found that PD-L1-positive tumors were more likely to have adverse pathological features including a late tumor stage (III or IV), high International Society of Urological Pathology (ISUP) grade (III or IV), larger tumor size, and a higher risk of cancer-specific mortality for patients

Summary

Introduction

Programmed death ligand-1 (PD-L1), a promising antitumor target, has proven clinical value against many malignancies. The PD-L1 content of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and its correlation with clinical outcomes remain unclear. Xp11.2 RCC is characterized by several translocations on chromosome Xp11.2, resulting in gene fusion between TFE3 and at least six possible partners[4,5,6] As it is a rare RCC subtype, the best treatment for Xp11.2 RCC has not been defined. We sought to investigate the levels of PD-L1 expression and its correlation with clinical outcome in a series of patients with Xp11.2 RCC that was histologically confirmed using TFE3 break-apart fluorescence in situ hybridization (FISH). (indicated by the respective arrows) and normal co-hybridization signals (yellow arrows) indicate that one X chromosome harbors the translocation and the other is normal in a female patient (×1000). (B) Separate red and green signals (indicated by the respective arrows) indicate that the only X chromosome harbors the translocation in a male patient (×1000); TFE3, transcription factor E3

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