This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Báez, A. Articles by Muñoz-Antonia, T. Search for Related Content PubMed PubMed Citation Articles by Báez, A. Articles by Muñoz-Antonia, T.

Differences in Smad4 Expression in Human Papillomavirus Type 16–Positive and Human Papillomavirus Type 16–Negative Head and Neck Squamous Cell Carcinoma

Authors' Affiliations: Departments of ¹ Otolaryngology-Head and Neck Surgery, ² Pharmacology and ³ Pathology, University of Puerto Rico School of Medicine, San Juan, Puerto Rico and Departments of ⁴ Interdisciplinary Oncology, ⁵ Molecular Oncology Program, and ⁶ Biostatistics and Informatics Core, H Lee Moffitt Cancer Center Research Institute, Tampa, Florida

Requests for reprints: Adriana Báez, Department of otolaryngology, School of Medicine, University of Puerto Rico, P.O. Box 365067, San Juan, PR 00936-5067. Phone: 787-758-2525; Fax: 1-787-759-6722; E-mail: abaez{at}rcm.upr.edu.

The SMADs are a group of interrelated proteins that mediate transforming growth factor ß (TGF-ß) signaling. Upon TGF-ß binding the TGF-ß type I receptor phosphorylates Smad2 and Smad3, which then complex with Smad4 and translocate to the nucleus, with subsequent activation of target genes. Disruption of TGF-ß signaling is thought to contribute to the development of head and neck squamous cell carcinomas (HNSCC). Alterations in the function of the DPC4/Smad4 tumor suppressor gene have been found to inactivate TGF-ß signaling in several tumor types. For example, DPC4/Smad4 is lost or mutated in colorectal, pancreatic, and esophageal cancers. In addition, DPC4/Smad4 transcriptional activity and TGF-ß ability to inhibit DNA synthesis is blocked by the E7 protein of the human papillomavirus type 16 (HPV16) in cervical carcinoma cell lines. HPV16 infection is a risk factor for the development of a subset of HNSCC. This study was undertaken to investigate a potential correlation between expression of components of the TGF-ß signaling pathway and HPV16 status in HNSCC tumors. We examined the expression of TGF-ß signaling proteins Smad2, Smad2-P, and Smad4 by immunohistochemistry in 27 HPV16-negative and 16 HPV16-positive HNSCCs. We compared the expression patterns and assessed their relationship to HPV16 status. No significant differences were detected between HPV16-positive and HPV16-negative tumors in the expression of Smad2 and Smad2-P. Smad4 expression, however, was decreased in 56% of the HPV16-positive tumors and in 39% of HPV16-negative tumors. This difference was statistically significant (P = 0.01) suggesting that loss of Smad4 expression may be involved in HPV16-induced carcinogenesis of HNSCC.

Key Words: Head and Neck Cancer • Smad4 • DNA tumor viruses • Signal transduction pathways • Head and neck/oral cancers