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J Cancer. 2014 Jan 24;5(3):166-72. doi: 10.7150/jca.8167. eCollection 2014.

PD-L1 Expression in Clear Cell Renal Cell Carcinoma: An Analysis of Nephrectomy and Sites of Metastases.

Author information

1
1. Departments of Medicine, Yale University School of Medicine, New Haven, CT, USA.
2
2. Department of Urology, Yale University School of Medicine, New Haven, CT, USA.
3
1. Departments of Medicine, Yale University School of Medicine, New Haven, CT, USA ; 3. Department of Biology, School of Health and Natural Sciences, University of Saint Joseph, West Hartford, CT, USA.
4
4. Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
5
5. Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.

Abstract

BACKGROUND:

Expression of programmed death ligand (PD-L1/B7-H1/CD274) represents a mechanism of immune escape for renal cell carcinoma (RCC) cells. Drugs blocking PD-L1 or its receptor are in clinical development and early data suggests that tumor PD-L1 expression may predict response.

PATIENTS AND METHODS:

A tissue microarray (TMA) consisting of four biopsy cores from 34 matched pairs of nephrectomy and metastatic sites of clear cell RCC was used to assess PD-L1 expression by quantitative immunofluorescence. Assessment of intra- and inter-tumor heterogeneity and primary and metastatic tumor expression was performed using a method of Automated Quantitative Analysis (AQUA).

RESULTS:

The median AQUA scores were higher in metastatic than primary specimens (P < 0.0001). The correlation between PD-L1 expression in matched primary and metastatic specimens was weak (R= 0.24). Within a given tumor, variable PD-L1 staining heterogeneity was seen, however the degree of heterogeneity was similar in primary and metastatic sites (P = 0.482).

CONCLUSIONS:

The weak correlation between PD-L1 expression in primary and metastatic sites for a given patient suggests that expression in nephrectomy specimens cannot be used to select metastatic RCC patients for PD-L1 and PD-1 inhibitors. The intra-tumor heterogeneity seen in both primary and metastatic specimens indicates that a single core biopsy might not be sufficient to determine PD-L1 expression.

KEYWORDS:

PD-L1; renal cell carcinoma

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