BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Ariel L Hernandez; Ying Wang; Hilary L Somerset; Stephen B Keysar; Dara L Aisner; Carrie Marshall; Daniel W Bowles; Sana D Karam; David Raben; Antonio Jimeno; Marileila Varella-Garcia; Xiao-Jing Wang Journal: Mol Carcinog Date: 2019-01-16 Impact factor: 4.784
Authors: Hiroyuki Ozawa; Ruchira S Ranaweera; Evgeny Izumchenko; Eugene Makarev; Alex Zhavoronkov; Elana J Fertig; Jason D Howard; Ana Markovic; Atul Bedi; Rajani Ravi; Jimena Perez; Quynh-Thu Le; Christina S Kong; Richard C Jordan; Hao Wang; Hyunseok Kang; Harry Quon; David Sidransky; Christine H Chung Journal: Clin Cancer Res Date: 2017-05-18 Impact factor: 12.531