CD70 expression patterns in renal cell carcinoma

Abstract

CD70 is up-regulated in several malignancies, where it induces cytotoxic effects on B and T lymphocytes, leading to immune escape. Novel therapeutic agents targeting CD70 have entered clinical trials. We characterized expression of CD70 protein in renal cell carcinoma specimens of various histologic subtypes and assessed their prognostic value and association with clinical/pathologic variables. We used tissue microarrays containing 330 cases using a novel fluorescent immunohistochemistry-based method of Automated Quantitative Analysis of in situ protein expression. The mean expression of CD70 was almost twice as high in tumors relative to normal tissue (P < .0001). When broken into subsets, CD70 was higher in sarcomatoid and clear cell tumors (P < .0001) and was variably elevated in oncocytomas and some papillary tumors. No association was found between CD70 expression and stage or grade. High CD70 expression was associated with decreased survival on univariate analysis in the clear cell subset of renal cell carcinoma; however, it did not retain significance on multivariate analysis. Given the elevated expression of CD70 in clear cell, sarcomatoid, and some papillary tumors, our findings suggest that CD70 might be a good drug target in renal cell carcinoma. Additional studies are warranted to assess the association between expression of CD70 and response to therapy with CD70-targeting drugs in renal cell carcinoma.

Copyright © 2012 Elsevier Inc. All rights reserved.

Figures

Figure 1

Cytoplasmic CD70 expression in RCC histospots using Cytokeratin to define the tumor mask, DAPI to define the nuclear compartment, and Cy5 for the target. Merged images displayed in the left half of panels A and B show CD70 within the nuclear compartment and within the cytoplasmic compartment within the tumor mask at 10× magnification. The right half of the panels shows expression of CD70 at 60× magnification. Panel A shows a positive/high expression of CD70, while panel B depicts low expression levels.

Figure 2

A) Regression plot from the scores derived from the set of renal arrays for CD70. The Y-axis represents AQUA scores from one slide and the X axis from the second slide. Each array contains histospots from the same patients, taken from different areas of the tumor. The linear regression line has an r-value of 0.76 (P <0.0001). B) Box plot representing the AQUA scores for CD70 expression levels in the five histological types of renal cell carcinoma, reflecting the results from the ANOVA analysis. The horizontal bars represent the 95th, 75th, 50th, 25th, and 5tth percentiles (top to bottom), and the notch demonstrates the 95% confidence interval around the mean. Clear Cell and Sarcomatoids show the highest level of expression of CD70. There is also a significant subgroup of clear cell and sarcomatoid tumors with low levels of expression of CD70. The overall ANOVA P-value was <0.0001. T-tests between individual subsets are shown in supplementary table 1. The number of tumors in each subset is listed in parentheses.