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Sarcomatoid renal cell carcinoma is an example of epithelial–mesenchymal transition
  1. Joanna L Conant1,
  2. Zhihua Peng2,
  3. Mark F Evans2,
  4. Shelly Naud3,
  5. Kumarasen Cooper2
  1. 1University of Vermont College of Medicine, Burlington, Vermont, USA
  2. 2Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont, USA
  3. 3Medical Biostatistics, University of Vermont College of Medicine, Burlington, Vermont, USA
  1. Correspondence to Joanna Conant, University of Vermont College of Medicine, 89 Beaumont Avenue, Given Box B19, Burlington, VT 05405, USA; joanna.conant{at}uvm.edu

Abstract

Background Sarcomatoid renal cell carcinomas (SRCC) are composed of two cell populations, a sarcomatous component (SC) and a carcinomatous component (CC). SRCC are particularly aggressive and often present at an advanced stage at diagnosis. Epithelial–mesenchymal transition (EMT) has been proposed as a mechanism for the development of SC from CC.

Aims and methods E- to N-cadherin switching, localisation of β-catenin, and expression of Snail and secreted protein acidic and rich in cysteine (SPARC) (markers of EMT) were studied to determine whether SRCC is an example of EMT. Expression of these markers was analysed by immunohistochemistry on 21 cases of SRCC that had both SC and CC and scored according to intensity and extent.

Results E-cadherin expression was decreased in SC (Wilcoxon signed-rank test, p=0.0004) while N-cadherin expression was high in both components (p=0.46). Membranous β-catenin expression was decreased in SC (p<0.0001) while cytoplasmic expression was increased (p=0.0002). Snail and SPARC had higher expression in SC (p=0.002 and p<0.0001, respectively). When the scores were dichotomised into low and high expression levels, the results using McNemar's test substantiated the above results.

Conclusions E- to N-cadherin switching, dissociation of β-catenin from the membrane, and increased expression of Snail and SPARC in SC indicate that SRCC is an example of EMT. High expression of N-cadherin and Snail in CC suggest early involvement in initiating EMT. Once EMT is established, loss of E-cadherin, release of β-catenin into the cytoplasm, and expression of SPARC correspond with mesenchymal phenotypic expression.

  • Renal cell carcinoma
  • epithelial–mesenchymal transition
  • immunohistochemistry
  • neoplasms
  • surgical pathology
  • methodology
  • in situ hybridisation
  • molecular pathology
  • fish
  • HPV
  • cervical cancer
  • papilloma viruses
  • gynaecological pathology
  • soft tissue tumours
  • histopathology

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Footnotes

  • Competing interests None declared.

  • Ethics approval This study was conducted with the approval of the University of Vermont Institutional Review Board and Vermont Cancer Center Protocol Review Committee.

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

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