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Ujjal K. Bhawal, BDS, PhD; Masaru Sugiyama, DDS, PhD; Yuji Nomura, DDS, PhD; Hiroki Kuniyasu, MD, PhD; Keiichi Tsukinoki, DDS, PhD

Arch Otolaryngol Head Neck Surg. 2008;134(10):1055-1059.

Objective  To confirm the expression of 14-3-3 sigma in oral malignant lesions and in adjacent nonmalignant oral epithelium to provide a clue to the involvement in the cell cycle progression and note any association with human papillomavirus (HPV) status. 14-3-3 Sigma plays important roles in a wide range of vital regulatory processes, including signal transduction, apoptosis, cell cycle progression, and DNA replication. 14-3-3 Sigma is an exclusive epithelial marker, and data on its expression in different malignancies are very scarce.

Design  Western blotting, immunohistochemical analysis, and polymerase chain reaction were performed.

Setting  An academic university laboratory.

Patients  Adults with known oral squamous cell carcinomas (SCCs) that were surgically resected.

Main Outcome Measures  The DNA of HPV-16 E6 was detected by polymerase chain reaction, and protein expression of 14-3-3 sigma was evaluated by Western blot and immunohistochemical analysis.

Results  The immunoreactive 14-3-3 sigma protein was detected mainly in the cytoplasm of differentiated squamous cells of oral SCC lesions as well as adjacent nonmalignant squamous mucosa. Immunoreactivity for 14-3-3 sigma was observed in 93% of SCC lesions (27 of 29), including HPV-negative cases. No significant association was observed between 14-3-3 sigma expression and clinicopathologic parameters. A statistically significant correlation was found between 14-3-3 sigma protein expression and the Ki-67 labeling index. 14-3-3 Sigma expression was correlated inversely with HPV-16 E6.

Conclusion  These findings suggest that 14-3-3 sigma may act as a negative regulator of the cell cycle progression in oral SCC.

Author Affiliations: Department of Diagnostic Science, Division of Pathology & High Tech Research Center, Kanagawa Dental College, Yokosuka (Drs Bhawal and Tsukinoki); Department of Molecular Pathology, Nara Medical University, Kashihara (Drs Bhawal and Kuniyasu); and Department of Oral Health Research, School for Oral Health Science, Faculty of Dentistry (Dr Sugiyama), and Department of Biomaterials Science, Graduate School of Biomedical Sciences (Dr Nomura), Hiroshima University, Hiroshima; Japan.

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