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Sarcomatoid conversion of clear cell renal cell carcinoma in relation to epithelial-to-mesenchymal transition.

Boström, Anna-Karin LU ; Möller, Christina LU ; Nilsson, Elise LU ; Elfving, Peter LU ; Axelson, Håkan LU and Johansson, Martin LU (2012) In Human Pathology 43. p.708-719
Abstract
Approximately 8% of clear cell renal cell carcinoma cases contain regions of radically different morphology, demonstrating a mesenchymal appearance histologically resembling sarcomas. These biphasic neoplasms are called sarcomatoid clear cell renal cell carcinoma. Patients diagnosed with sarcomatoid clear cell renal cell carcinoma face a considerably worse prognosis due to an increased propensity for metastasis. In the present study we investigate whether the sarcomatoid conversion of clear cell renal cell carcinoma could be interpreted as linked to the process of epithelial-mesenchymal transition. Using 6 biphasic clear cell renal cell carcinoma cases we show that sarcomatoid clear cell renal cell carcinoma shares characteristic markers... (More)
Approximately 8% of clear cell renal cell carcinoma cases contain regions of radically different morphology, demonstrating a mesenchymal appearance histologically resembling sarcomas. These biphasic neoplasms are called sarcomatoid clear cell renal cell carcinoma. Patients diagnosed with sarcomatoid clear cell renal cell carcinoma face a considerably worse prognosis due to an increased propensity for metastasis. In the present study we investigate whether the sarcomatoid conversion of clear cell renal cell carcinoma could be interpreted as linked to the process of epithelial-mesenchymal transition. Using 6 biphasic clear cell renal cell carcinoma cases we show that sarcomatoid clear cell renal cell carcinoma shares characteristic markers associated with loss of von Hippel-Lindau tumor suppressor with conventional clear cell renal cell carcinoma and also exhibits a markedly higher proliferative index. Furthermore the sarcomatoid elements demonstrate an enhanced expression of epithelial-mesenchymal transition related mesenchymal markers as compared with the clear cell renal cell carcinoma counterparts. We further selected a representative case, clinically demonstrating direct overgrowth of the sarcomatoid component into the liver and colon, for extended immunohistochemical characterization, resulting in a further set of positive and negative epithelial-mesenchymal transition markers as well as pronounced transforming growth factor β positivity, indicating that sarcomatoid clear cell renal cell carcinoma may be associated to epithelial-mesenchymal transition. Transforming growth factor β1 exposure of in vitro cultured primary clear cell renal cell carcinoma cells resulted in cells adopting a mesenchymal morphology similar to sarcomatoid clear cell renal cell carcinoma. Corresponding changes in RNA levels for key epithelial-mesenchymal transition markers were also seen. We therefore suggest that sarcomatoid clear cell renal cell carcinoma morphologically and immunohistochemically may represent a completed epithelial-mesenchymal transition and that transforming growth factor β1 could be an important driving force during the sarcomatoid transdifferentiation of clear cell renal cell carcinoma. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Pathology
volume
43
pages
708 - 719
publisher
Elsevier
external identifiers
  • wos:000303288600012
  • pmid:21992819
  • scopus:84859914084
ISSN
1532-8392
DOI
10.1016/j.humpath.2011.06.019
language
English
LU publication?
yes
id
af4bbeb2-4a30-466b-a16e-b78f57dbad5f (old id 2200546)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21992819?dopt=Abstract
date added to LUP
2011-11-02 10:08:39
date last changed
2017-03-12 04:17:42
@article{af4bbeb2-4a30-466b-a16e-b78f57dbad5f,
  abstract     = {Approximately 8% of clear cell renal cell carcinoma cases contain regions of radically different morphology, demonstrating a mesenchymal appearance histologically resembling sarcomas. These biphasic neoplasms are called sarcomatoid clear cell renal cell carcinoma. Patients diagnosed with sarcomatoid clear cell renal cell carcinoma face a considerably worse prognosis due to an increased propensity for metastasis. In the present study we investigate whether the sarcomatoid conversion of clear cell renal cell carcinoma could be interpreted as linked to the process of epithelial-mesenchymal transition. Using 6 biphasic clear cell renal cell carcinoma cases we show that sarcomatoid clear cell renal cell carcinoma shares characteristic markers associated with loss of von Hippel-Lindau tumor suppressor with conventional clear cell renal cell carcinoma and also exhibits a markedly higher proliferative index. Furthermore the sarcomatoid elements demonstrate an enhanced expression of epithelial-mesenchymal transition related mesenchymal markers as compared with the clear cell renal cell carcinoma counterparts. We further selected a representative case, clinically demonstrating direct overgrowth of the sarcomatoid component into the liver and colon, for extended immunohistochemical characterization, resulting in a further set of positive and negative epithelial-mesenchymal transition markers as well as pronounced transforming growth factor β positivity, indicating that sarcomatoid clear cell renal cell carcinoma may be associated to epithelial-mesenchymal transition. Transforming growth factor β1 exposure of in vitro cultured primary clear cell renal cell carcinoma cells resulted in cells adopting a mesenchymal morphology similar to sarcomatoid clear cell renal cell carcinoma. Corresponding changes in RNA levels for key epithelial-mesenchymal transition markers were also seen. We therefore suggest that sarcomatoid clear cell renal cell carcinoma morphologically and immunohistochemically may represent a completed epithelial-mesenchymal transition and that transforming growth factor β1 could be an important driving force during the sarcomatoid transdifferentiation of clear cell renal cell carcinoma.},
  author       = {Boström, Anna-Karin and Möller, Christina and Nilsson, Elise and Elfving, Peter and Axelson, Håkan and Johansson, Martin},
  issn         = {1532-8392},
  language     = {eng},
  pages        = {708--719},
  publisher    = {Elsevier},
  series       = {Human Pathology},
  title        = {Sarcomatoid conversion of clear cell renal cell carcinoma in relation to epithelial-to-mesenchymal transition.},
  url          = {http://dx.doi.org/10.1016/j.humpath.2011.06.019},
  volume       = {43},
  year         = {2012},
}