Virchows Archiv

, Volume 471, Issue 1, pp 107–115 | Cite as

Clear cell renal cell carcinoma: a comparative study of histological and chromosomal characteristics between primary tumors and their corresponding metastases

  • Julien Dagher
  • Solène-Florence Kammerer-Jacquet
  • Frédéric Dugay
  • Marion Beaumont
  • Alexandra Lespagnol
  • Laurence Cornevin
  • Grégory Verhoest
  • Karim Bensalah
  • Nathalie Rioux-Leclercq
  • Marc-Antoine Belaud-Rotureau
Original Article

Abstract

Clear cell renal cell carcinoma (ccRCC) has a poor prognosis with a 50% risk of metastases. Little is known about the phenotypic and molecular profiles of metastases regarding their corresponding primary tumors. This study aimed to screen phenotypic and genotypic differences between metastases and their corresponding primary tumors. We selected four cases with available frozen material. The histological, immunohistochemical (VEGFA, CD31, SMA, Ki67, p53, PAR-3), FISH (VHL gene), next-generation sequencing (VHL and c-MET genes), multiplex ligation-dependent probe amplification, and array-(comparative genomic hybridization) CGH analyses were realized. Metastases were nodal, hepatic (synchronous), adrenal, and pulmonary (metachronous). High-grade tumor cells were significantly more frequent in metastases (p = 0.019). Metastases and high-grade zones of primary tumors shared similar characteristics compared to low-grade zones: a lower microscopic vascular density (43.5 vs 382.5 vessels/mm2; p = 0.0027), a higher expression of VEGF (73 vs 10%, p = 0.045), Ki67 (37.6 vs 8.3%; p = 0.011), and p53 (54 vs 10.6%; p = 0.081), and a cytoplasmic and membranous PAR-3 staining. Metastases exhibited more chromosomal imbalances than primary tumors in total (18.75 ± 6.8; p = 0.044) with more genomic gains (13.5 ± 7; p = 0.013). The loss of chromosome 9 and gain of Xq were found in both primary tumors and metastases but gains of loci or chromosomes 2p, 3q, 5, 8q, 12, and 20 were only found in metastases. The VHL gene status was similar in each tumor couple. Although metastases and primary tumors share common histological features, this study highlights chromosomal differences specific to metastases which could be involved in ccRCC metastatic evolution.

Keywords

Clear cell renal cell carcinoma Metastasis Chromosome CGH 

Notes

Compliance with ethical standards

Human samples were obtained from the processing of biological samples through the Centre de Ressources Biologiques (CRB) Santé of Rennes BB-0033-00056. The research protocol was conducted under French legal guidelines and fulfilled the requirements of the local institutional ethics committee. Informed consent was signed from each patient.

Funding

No industry funds were used.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Julien Dagher
    • 1
    • 2
  • Solène-Florence Kammerer-Jacquet
    • 1
    • 2
  • Frédéric Dugay
    • 1
    • 3
  • Marion Beaumont
    • 1
    • 3
  • Alexandra Lespagnol
    • 4
  • Laurence Cornevin
    • 3
  • Grégory Verhoest
    • 5
  • Karim Bensalah
    • 5
  • Nathalie Rioux-Leclercq
    • 1
    • 2
  • Marc-Antoine Belaud-Rotureau
    • 1
    • 3
  1. 1.IRSET INSERM UMR 1085Faculté de Médecine de Rennes 1RennesFrance
  2. 2.Service d’Anatomie et Cytologie PathologiquesUniversité de Rennes 1RennesFrance
  3. 3.Service de Cytogénétique et Biologie CellulaireUniversité de Rennes 1RennesFrance
  4. 4.Service de Génétique Moléculaire et GénomiqueUniversité de Rennes 1RennesFrance
  5. 5.Service d’UrologieUniversité de Rennes 1RennesFrance

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