Alterations of Smad expression and activation in defining 2 subtypes of human head and neck squamous cell carcinoma
Article first published online: 24 JAN 2012
Copyright © 2012 Wiley Periodicals, Inc.
Head & Neck
Volume 35, Issue 1, pages 76–85, January 2013
How to Cite
Xie, W., Aisner, S., Baredes, S., Sreepada, G., Shah, R. and Reiss, M. (2013), Alterations of Smad expression and activation in defining 2 subtypes of human head and neck squamous cell carcinoma. Head Neck, 35: 76–85. doi: 10.1002/hed.22924
- Issue published online: 15 DEC 2012
- Article first published online: 24 JAN 2012
- Manuscript Accepted: 14 NOV 2011
- National Cancer Institute/National Institutes of Health. Grant Number: PHS R01 CA41556
- Biospecimen Repository and Immunohistochemistry and Imaging Shared Resources of The Cancer Institute of New Jersey
- transforming growth factor-β;
- head and neck cancer;
- tissue microarray
We postulated that disruptions of the canonical transforming growth factor-beta (TGF-β)/Smad signaling pathway might contribute to the development of head and neck squamous cell carcinoma (HNSCC).
A cohort of 798 HNSCC tumor samples from 346 patients were analyzed by immunohistochemistry (IHC) to define the pattern of expression of (phospho)Smad2, (phospho)Smad3, and Smad4.
We found that 19%, 40%, and 12% of HNSCC specimens failed to express pSmad2, pSmad3, or Smad4, respectively. Loss of Smad2/3 activation was observed in 8.5% of specimens. In addition, 4% of specimens failed to express only Smad4. Moreover, patients with pSmad2/3-negative tumors had a significantly better overall survival than that of those whose tumors expressed activated Smad2/3. In contrast, loss of Smad4 expression did not have prognostic significance.
Our results indicate that HNSCC in which Smad2/3 are inactivated or in which Smad4 expression is lost represent 2 distinct tumor subtypes with different clinical outcomes. © 2012 Wiley Periodicals, Inc. Head Neck, 2013