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Published on: February 8, 2018
CD70 expression patterns in renal cell carcinoma
Lucia B Jilaveanu1, Joshua Sznol, Saadia A Aziz
1Department of Medicine, Section of Medical Oncology, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA.
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.
Insights
CD70 is elevated in kidney tumors, particularly clear cell and sarcomatoid subtypes. This suggests CD70 may be a viable therapeutic target for renal cell carcinoma treatment.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- CD70 is upregulated in various cancers, promoting immune evasion by affecting lymphocytes.
- Targeting CD70 is a promising therapeutic strategy, with agents in clinical trials.
Purpose of the Study:
- To characterize CD70 protein expression in different renal cell carcinoma (RCC) subtypes.
- To evaluate the prognostic significance of CD70 expression in RCC.
- To explore associations between CD70 expression and clinical/pathologic variables.
Main Methods:
- Utilized tissue microarrays from 330 RCC cases.
- Employed a novel fluorescent immunohistochemistry-based Automated Quantitative Analysis (AQUA) for in situ protein expression.
- Analyzed CD70 expression across various RCC histologic subtypes.
Main Results:
- CD70 expression was significantly higher in tumor tissues compared to normal kidney tissue (P < .0001).
- Elevated CD70 levels were observed in clear cell and sarcomatoid RCC subtypes (P < .0001), and variably in oncocytomas and papillary tumors.
- High CD70 expression showed a trend towards decreased survival in clear cell RCC on univariate analysis but was not significant in multivariate analysis. No association with stage or grade was found.
Conclusions:
- CD70 is frequently overexpressed in several renal cell carcinoma subtypes, including clear cell and sarcomatoid.
- The elevated expression suggests CD70 is a potential therapeutic target for renal cell carcinoma.
- Further research is needed to correlate CD70 expression with treatment response to CD70-targeting therapies in RCC.
