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Intratumoural heterogeneity may hinder precision medicine strategies in patients with clear cell renal cell carcinoma
  1. Maria Rosaria Raspollini1,
  2. Ilaria Montagnani1,
  3. Rodolfo Montironi2,
  4. Francesca Castiglione1,
  5. Guido Martignoni3,
  6. Liang Cheng4,
  7. Antonio Lopez-Beltran5
  1. 1 Histopathology and Molecular Diagnostics, Universitary Hospital Careggi, Florence, Italy
  2. 2 Department of Biomedical Sciences and Public Health, Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy
  3. 3 Department of Pathology, Anatomic Pathology, University of Verona, Verona, Italy
  4. 4 Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
  5. 5 Department of Surgery, Unit of Anatomic Pathology, Cordoba University Medical School, Cordoba, Spain
  1. Correspondence to Dr Maria Rosaria Raspollini, Histopathology and Molecular Diagnostics, Universitary Hospital Careggi, Florence 30134, Italy; mariarosaria.raspollini{at}


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.

  • uropathology
  • carcinoma
  • molecular pathology

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  • Handling editor Runjan Chetty.

  • Contributors All the authors contributed to the manuscript.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.