TGF-β1, Smad-2/-3, Smad-1/-5/-8, and Smad-4 signaling factors are expressed in ameloblastomas, adenomatoid odontogenic tumors, and calcifying cystic odontogenic tumors: an immunohistochemical study
Version of Record online: 15 NOV 2012
© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
Journal of Oral Pathology & Medicine
Volume 42, Issue 5, pages 415–423, May 2013
How to Cite
J Oral Pathol Med (2012)
- Issue online: 22 APR 2013
- Version of Record online: 15 NOV 2012
- Manuscript Accepted: 2 OCT 2012
- adenomatoid odontogenic tumor;
- calcifying cystic odontogenic tumor;
The TGF-β/Smad signaling pathway regulates diverse cellular functions, including tooth development, and is involved in numerous pathological processes such as tumorigenesis. The aim of this study was to investigate the immunoexpression of the TGF-β/Smad signaling pathway members in ameloblastoma (AM), calcifying cystic odontogenic tumor (CCOT), and adenomatoid odontogenic tumor (AOT).
Materials and methods
This retrospective cross-sectional study included 65 tissue specimens: 34 AMs, 13 CCOTs, and 18 AOTs. Serial sections were immunohistochemically stained with TGF-β1, Smad-4, Smad-1/-5/-8, and Smad-2/-3 antibodies, and a semiquantitative measurement of the positive cells was carried out by two oral pathologists using a 0–3 scale (0: no immunoreactivity, 1: <20% positive cells, 2: 20–50% positive cells, 3: >50% positive cells).
All biomarkers studied were found significantly decreased in AM compared to CCOT and AOT. AOT and CCOT expressed Smad-1/-5/-8 more strongly compared to AM (OR = 11.66, P < 0.001 and OR = 5.34, P = 0.013, respectively), and Smad-2/-3 immunostaining was found significantly increased in CCOT (OR = 10.42, P = 0.001) and AOT (OR = 5.16, P < 0.004) compared to AM. Similarly, Smad-4 was expressed more strongly in AOT and CCOT compared to AM (P = 0.001), while AOT demonstrated a fivefold higher chance to express TGF-β1 compared to AM (P = 0.011).
TGF-β/Smad signaling pathway is activated in AM, AOT, and CCOT. The statistically significant reduced TGF-β1/Smad immunoexpression in AM compared to AOT/CCOT could be associated with the more aggressive biological behavior of AM including increased cell proliferation and reduced apoptosis and differentiation. Thus, the biomarkers TGF-β, Smad-4, Smad-1/-5/-8, and Smad-2/-3 could serve as supplementary diagnostic indices between odontogenic tumors of high and low neoplastic dynamics.