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Sarcomatoid carcinoma represents a complete phenotype with various pathways of epithelial mesenchymal transition
  1. Chang Ohk Sung1,
  2. Hannah Choi2,
  3. Keun-Woo Lee3,
  4. Seok-Hyung Kim3
  1. 1Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  2. 2Kyunggi Girls’ High School, Gangnam-gu, Seoul, Korea
  3. 3Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  1. Correspondence to Professor Seok-Hyung Kim, Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong Gangnam-gu, Seoul 135-710, South Korea; platoshkim{at}daum.net

Abstract

Aims Sarcomatoid carcinoma (SC) is considered to be a result of the sarcomatoid change of epithelial carcinoma. However, epithelial–mesenchymal transition (EMT) in SC has been insufficiently studied.

Methods We evaluated the expression patterns of EMT-related phenotypic markers with transcription factors in 27 SCs originating from various organs, and we investigated the phenotypic characteristics of SCs classified as complete, incomplete or wild-type. We further analysed correlations between EMT-related phenotype markers and transcription factors.

Results Epithelial markers (E-cadherin, claudin-3 and claudin-4) were consistently down-regulated, whereas mesenchymal markers (S100A4, α-smooth muscle actin (SMA), vimentin, PDGFRα and β-catenin) were variously expressed except for vimentin. EMT-related transcription factors (SIP1, Snail1, Slug, Twist1, ZEP1 and Oct-4) also showed various expression patterns. The expression patterns of phenotypic markers showed that most SCs (22/27, 81.5%, 95% CI 65.8 to 97.1%) had complete EMT phenotypes, whereas the remaining 5 (18.5%, 95% CI 2.8 to 24.1%) were of incomplete type. Unsupervised hierarchical clustering analysis revealed that SCs were clustered into several subgroups by EMT-related protein expression pattern. Twist1 positivity was significantly concordant with α-SMA positivity (κ value: 0.908; 95% CI 0.73 to 1.00, p<0.001, adjusted p<0.001). The EMT phenotypes of SC were simple, with complete phenotype being the predominant form, and the morphological changes of the SCs were also relevant in terms of EMT.

Conclusions SC seems to be an irreversible, permanent change in the EMT phenomenon, with complete EMT phenotypes and various EMT-related pathways being involved in SC.

  • ONCOLOGY
  • MOLECULAR ONCOLOGY
  • HISTOPATHOLOGY
  • GASTROENTEROLOGY

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