Annals of Surgical Oncology

, Volume 16, Issue 7, pp 1997–2005

Expression of the Transcription Factor Snail and Its Target Gene Twist Are Associated with Malignancy in Pheochromocytomas


    • Department of SurgeryPhilipps-University Marburg
  • Emily P. Slater
    • Department of SurgeryPhilipps-University Marburg
  • Peter Langer
    • Department of SurgeryPhilipps-University Marburg
  • Malte Buchholz
    • Department of Internal Medicine, Division of Gastroenterology and EndocrinologyPhilipps-University Marburg
  • Annette Ramaswamy
    • Department of PathologyPhilipps-University Marburg
  • Martin K. Walz
    • Department of Surgery and Centre of Minimally Invasive SurgeryKliniken Essen-Mitte
  • Kurt W. Schmid
    • Institute of Pathology and NeuropathologyUniversity Hospital Essen, University of Duisburg-Essen
  • Georg Feldmann
    • Department of PathologyJohns Hopkins University School of Medicine
    • The Sol Goldman Pancreatic Cancer Research CenterJohns Hopkins University School of Medicine
  • Detlef K. Bartsch
    • Department of SurgeryPhilipps-University Marburg
  • Volker Fendrich
    • Department of SurgeryPhilipps-University Marburg
Endocrine Tumors

DOI: 10.1245/s10434-009-0480-y

Cite this article as:
Waldmann, J., Slater, E.P., Langer, P. et al. Ann Surg Oncol (2009) 16: 1997. doi:10.1245/s10434-009-0480-y



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.


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.


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.


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.

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© Society of Surgical Oncology 2009