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SIX1 protein expression selectively identifies blastemal elements in Wilms tumor.

Sehic, Daniel LU ; Karlsson, Jenny LU ; Sandstedt, Bengt and Gisselsson Nord, David LU (2012) In Pediatric Blood & Cancer 59(1). p.62-68
Abstract
BACKGROUND: Wilms tumor (WT) is the most common renal neoplasm in children. Histologically, most WTs consist of three tissue elements: blastema, epithelium, and stroma. Some cases also show diffuse or focal anaplastic features. Previous studies have shown that a predominance of blastemal cells in post-chemotherapy WT specimens is associated with a poor clinical course. However, there is currently no molecular marker for blastemal cells, and risk stratification for post-nephrectomy treatment is therefore often based on clinico-histological parameters alone. PROCEDURE: In the present study, three public gene expression microarray datasets, including 82 WTs and 8 normal fetal kidneys, were used to establish a consensus gene expression profile... (More)
BACKGROUND: Wilms tumor (WT) is the most common renal neoplasm in children. Histologically, most WTs consist of three tissue elements: blastema, epithelium, and stroma. Some cases also show diffuse or focal anaplastic features. Previous studies have shown that a predominance of blastemal cells in post-chemotherapy WT specimens is associated with a poor clinical course. However, there is currently no molecular marker for blastemal cells, and risk stratification for post-nephrectomy treatment is therefore often based on clinico-histological parameters alone. PROCEDURE: In the present study, three public gene expression microarray datasets, including 82 WTs and 8 normal fetal kidneys, were used to establish a consensus gene expression profile of WT. By bioinformatic analyses, 17 genes overexpressed in WT compared to fetal kidney were then selected for evaluation of their protein expression in WT cell lines and in the different histological components in paraffin-embedded WT tissue sections by immunofluorescence. RESULTS: Most of the evaluated proteins were expressed in all three common histological components. A prominent exception was SIX1, being expressed predominantly in blastemal elements in 24/25 pediatric cases containing blastema. Anaplastic elements exhibited highly variable SIX1-positivity. The SIX2 protein, known to be co-expressed with SIX1 during nephrogenesis, only exhibited blastemal-predominant expression in half of the SIX2 evaluated cases. CONCLUSIONS: Genes highly expressed in WT compared to fetal kidney are generally overexpressed in all of the three common WT tissue elements. An exception is the predominant expression of SIX1 in blastemal cells, hereby identifying this protein as a candidate marker for blastema. Pediatr Blood Cancer © 2011 Wiley Periodicals, Inc. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pediatric Blood & Cancer
volume
59
issue
1
pages
62 - 68
publisher
John Wiley and Sons Inc.
external identifiers
  • wos:000304142700013
  • pmid:22180226
  • scopus:84861203782
ISSN
1545-5017
DOI
10.1002/pbc.24025
language
English
LU publication?
yes
id
8cca4a39-ea50-4737-9545-15a578a246ec (old id 2273898)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22180226?dopt=Abstract
date added to LUP
2012-01-03 20:09:01
date last changed
2017-07-09 04:30:51
@article{8cca4a39-ea50-4737-9545-15a578a246ec,
  abstract     = {BACKGROUND: Wilms tumor (WT) is the most common renal neoplasm in children. Histologically, most WTs consist of three tissue elements: blastema, epithelium, and stroma. Some cases also show diffuse or focal anaplastic features. Previous studies have shown that a predominance of blastemal cells in post-chemotherapy WT specimens is associated with a poor clinical course. However, there is currently no molecular marker for blastemal cells, and risk stratification for post-nephrectomy treatment is therefore often based on clinico-histological parameters alone. PROCEDURE: In the present study, three public gene expression microarray datasets, including 82 WTs and 8 normal fetal kidneys, were used to establish a consensus gene expression profile of WT. By bioinformatic analyses, 17 genes overexpressed in WT compared to fetal kidney were then selected for evaluation of their protein expression in WT cell lines and in the different histological components in paraffin-embedded WT tissue sections by immunofluorescence. RESULTS: Most of the evaluated proteins were expressed in all three common histological components. A prominent exception was SIX1, being expressed predominantly in blastemal elements in 24/25 pediatric cases containing blastema. Anaplastic elements exhibited highly variable SIX1-positivity. The SIX2 protein, known to be co-expressed with SIX1 during nephrogenesis, only exhibited blastemal-predominant expression in half of the SIX2 evaluated cases. CONCLUSIONS: Genes highly expressed in WT compared to fetal kidney are generally overexpressed in all of the three common WT tissue elements. An exception is the predominant expression of SIX1 in blastemal cells, hereby identifying this protein as a candidate marker for blastema. Pediatr Blood Cancer © 2011 Wiley Periodicals, Inc.},
  author       = {Sehic, Daniel and Karlsson, Jenny and Sandstedt, Bengt and Gisselsson Nord, David},
  issn         = {1545-5017},
  language     = {eng},
  number       = {1},
  pages        = {62--68},
  publisher    = {John Wiley and Sons Inc.},
  series       = {Pediatric Blood & Cancer},
  title        = {SIX1 protein expression selectively identifies blastemal elements in Wilms tumor.},
  url          = {http://dx.doi.org/10.1002/pbc.24025},
  volume       = {59},
  year         = {2012},
}