Loss of 14-3-3 sigma protein expression and presence of human papillomavirus type 16 E6 in oral squamous cell carcinoma

Abstract

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.