Radiogenomics of clear cell renal cell carcinoma: associations between CT imaging features and mutations

Radiology. 2014 Feb;270(2):464-71. doi: 10.1148/radiol.13130663. Epub 2013 Oct 28.

Abstract

Purpose: To investigate associations between computed tomographic (CT) features of clear cell renal cell carcinoma (RCC) and mutations in VHL, PBRM1, SETD2, KDM5C, or BAP1 genes.

Materials and methods: The institutional review board approved this retrospective, hypothesis-generating study of 233 patients with clear cell RCC and waived the informed consent requirement. The study was HIPAA compliant. Three radiologists independently reviewed pretreatment CT images of all clear cell RCCs without knowledge of their genomic profile. One radiologist measured largest diameter and enhancement parameters of each clear cell RCC. Associations between CT features and mutations in VHL, PBRM1, SETD2, KDM5C, and BAP1 genes were tested by using the Fisher exact test. Associations between mutations and size and enhancement were assessed by using the independent t test. Interreader agreement was calculated by using the Fleiss κ.

Results: Mutation frequencies among clear cell RCCs were as follows: VHL, 53.2% (124 of 233); PBRM1, 28.8% (67 of 233); SETD2, 7.3% (17 of 233); KDM5C, 6.9% (16 of 233); and BAP1, 6.0% (14 of 233). Mutations of VHL were significantly associated with well-defined tumor margins (P = .013), nodular tumor enhancement (P = .021), and gross appearance of intratumoral vascularity (P = .018). Mutations of KDM5C and BAP1 were significantly associated with evidence of renal vein invasion (P = .022 and .046, respectively). The genotype of solid clear cell RCC differed significantly from the genotype of multicystic clear cell RCC. While mutations of SETD2, KDM5C, and BAP1 were absent in multicystic clear cell RCC, mutations of VHL (P = .016) and PBRM1 (P = .017) were significantly more common among solid clear cell RCC. Interreader agreement for CT feature assessments ranged from substantial to excellent (κ = 0.791-0.912).

Conclusion: This preliminary radiogenomics analysis of clear cell RCC revealed associations between CT features and underlying mutations that warrant further investigation and validation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carcinoma, Renal Cell / diagnostic imaging*
  • Carcinoma, Renal Cell / genetics*
  • Contrast Media
  • DNA-Binding Proteins
  • Female
  • Genotype
  • Histone Demethylases
  • Histone-Lysine N-Methyltransferase / genetics
  • Humans
  • Kidney Neoplasms / diagnostic imaging*
  • Kidney Neoplasms / genetics*
  • Male
  • Mutation*
  • Nuclear Proteins / genetics
  • Oxidoreductases, N-Demethylating / genetics
  • Phenotype
  • Polymerase Chain Reaction
  • Retrospective Studies
  • Tomography, X-Ray Computed / methods*
  • Transcription Factors / genetics
  • Tumor Suppressor Proteins / genetics
  • Ubiquitin Thiolesterase / genetics
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics

Substances

  • BAP1 protein, human
  • Contrast Media
  • DNA-Binding Proteins
  • Nuclear Proteins
  • PBRM1 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Histone Demethylases
  • KDM5C protein, human
  • Oxidoreductases, N-Demethylating
  • Histone-Lysine N-Methyltransferase
  • SETD2 protein, human
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Ubiquitin Thiolesterase
  • VHL protein, human

Supplementary concepts

  • Clear-cell metastatic renal cell carcinoma