CD70 is Consistently Expressed in Primary and Metastatic Clear Cell Renal Cell Carcinoma

Clin Genitourin Cancer. 2024 Apr;22(2):347-353. doi: 10.1016/j.clgc.2023.12.003. Epub 2023 Dec 13.

Abstract

Background: CD70 is commonly overexpressed in renal cell carcinoma and is minimally expressed in normal human tissue, making it a potential therapeutic target for patients with advanced renal cell carcinoma. The expression frequency of CD70 in metastatic renal cell carcinoma is not well established.

Materials and methods: We assessed CD70 immunohistochemistry in 391 primary renal tumors and 72 metastatic renal cell carcinomas on a tissue microarray including 26 sets of paired primary and metastatic tumors.

Results: CD70 was frequently overexpressed in clear cell carcinoma, with a significantly lower expression rate in papillary renal cell carcinoma (P < .0001). No expression of CD70 was detected in other types of renal tumors and normal renal parenchyma. In clear cell renal cell carcinoma, CD70 expression was significantly correlated with hypoxia pathway proteins, corroborating with a recent study suggesting that CD70 is a downstream target gene of hypoxia-inducible factor. While higher expression levels were observed in males and non-Caucasians, CD70 expression was not associated with tumor grade, sarcomatoid differentiation, stage, or cancer-specific survival. Further, analysis of 26 paired primary and metastatic tumors from same individuals revealed a concordance rate of 85%.

Conclusion: Our findings validated CD70 as a promising therapeutic target for patients with metastatic clear cell renal cell carcinoma. The utility of primary tumor tissue as surrogate samples for metastatic clear cell carcinoma awaits future CD70-targeted clinical trials.

Keywords: CD70; Clear cell; Hypoxia; Renal cell carcinoma; Targeted therapy.

MeSH terms

  • Biomarkers, Tumor
  • CD27 Ligand / metabolism
  • Carcinoma, Renal Cell* / drug therapy
  • Humans
  • Hypoxia
  • Kidney / pathology
  • Kidney Neoplasms* / drug therapy
  • Male

Substances

  • Biomarkers, Tumor
  • CD70 protein, human
  • CD27 Ligand

Supplementary concepts

  • Clear-cell metastatic renal cell carcinoma