J Cancer 2014; 5(3):166-172. doi:10.7150/jca.8167
PD-L1 Expression in Clear Cell Renal Cell Carcinoma: An Analysis of Nephrectomy and Sites of Metastases
1. Departments of Medicine, Yale University School of Medicine, New Haven, CT, USA
2. Department of Urology, 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. Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
5. Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA
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
Jilaveanu LB, Shuch B, Zito CR, Parisi F, Barr M, Kluger Y, Chen L, Kluger HM. PD-L1 Expression in Clear Cell Renal Cell Carcinoma: An Analysis of Nephrectomy and Sites of Metastases. J Cancer 2014; 5(3):166-172. doi:10.7150/jca.8167. Available from http://www.jcancer.org/v05p0166.htm