Expression of the transcription factor snail and its target gene twist are associated with malignancy in pheochromocytomas.
BACKGROUND
One of the best known functions of the zinc-finger transcription factor Snail is to induce epithelial-mesenchymal transition (EMT). Twist, a target genes of Snail, is known to promote the development of distant metastases in mice. Increasing evidence suggests that EMT plays a pivotal role in tumor progression and metastatic spread.


METHODS
Snail, Twist, and E-cadherin expression were assessed by immunohistochemistry and real-time quantitative reverse transcriptase-polymerase chain reaction in 12 malignant and 35 benign pheochromocytomas (PCC). Data were correlated with clinical characteristics and genetics.


RESULTS
We found Snail expression in 13 (28%) of 47 primary PCC samples. Twist was expressed in 31 (66%) of 47 cases. Only one of 47 PCC showed E-cadherin expression. We observed Snail expression in 7 (58%) of 12 malignant PCC, whereas only 6 (17%) of 35 apparently benign PCC revealed Snail expression (P = 0.01). Furthermore, 11 (92%) of 12 malignant PCC, but only 20 (57%) of 35 benign PCC, revealed Twist expression (P = 0.03). Interestingly, all five metastases showed Snail and Twist expression. In normal adrenal medulla, Snail, Twist, and E-cadherin expression could not be detected.


CONCLUSIONS
We describe for the first time that EMT markers Snail and Twist are expressed in PCC and that their expression is associated with malignancy. Our study supports a role for EMT in the malignant transformation of PCC.
Department of Surgery, Philipps-University Marburg, Marburg, Germany. jwaldman@med.uni-marburg.de
Jens
J
Waldmann
Emily P
EP
Slater
Peter
P
Langer
Malte
M
Buchholz
Annette
A
Ramaswamy
Martin K
MK
Walz
Kurt W
KW
Schmid
Georg
G
Feldmann
Detlef K
DK
Bartsch
Volker
V
Fendrich
D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000503:physiopathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D010673:Pheochromocytoma / Q000235:genetics* / Q000503:physiopathology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D051879:Twist-Related Protein 1 / Q000096:biosynthesis / Q000235:genetics*; D055815:Young Adult
D014408:Biomarkers, Tumor; D015820:Cadherins; D009687:Nuclear Proteins; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1