Intratumoural heterogeneity may hinder precision medicine strategies in patients with clear cell renal cell carcinoma

J Clin Pathol. 2018 May;71(5):467-471. doi: 10.1136/jclinpath-2017-204931. Epub 2018 Jan 9.


Clear cell renal cell carcinoma (ccRCC) is an heterogeneous tumour at architectural, cellular and molecular level, a reason why the 2014 International Society of Urological Pathology consensus recommended wide sampling of RCC masses to include at least 1 block/cm of tumour together with perpendicular sections of the tumour/perinephric fat interface and the tumour/renal sinus interface. Intratumoural molecular heterogeneity may be a limitation at the moment of defining precision medicine strategies based on gene mutation status. This study analyses the presence of any mutation of KRAS, NRAS, BRAF, PIK3CA, ALK, ERBB2, DDR2, MAP2K1, RET and EGFR genes in 20 tissue blocks from a case of ccRCC and its metastasis. We observed the presence of the mutation at pH1047R of PIK3CA gene in five samples of the tumour, while the remaining 15 samples did not show any mutation at PIK3CA or any other investigated gene. There is a great need to develop novel RCC sampling strategies to overcome tumour heterogeneity prior to define precision oncology strategies.

Keywords: carcinoma; molecular pathology; uropathology.

Publication types

  • Case Reports

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / secondary
  • Carcinoma, Renal Cell / therapy
  • DNA Mutational Analysis
  • Genetic Heterogeneity*
  • Genetic Predisposition to Disease
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / therapy
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Mutation*
  • Nephrectomy
  • Phenotype
  • Precision Medicine*
  • Predictive Value of Tests


  • Antineoplastic Agents
  • Biomarkers, Tumor