2000 Pilot Grant Award – Final Report
- Analysis of p63 isoform expression in normal, diseased, and malignant mucosa of the head and neck
- Joseph C. Sniezek MD, Keith E. Matheny MD, Matthew D. Westfall, Jennifer A. Pietenpol PhD
- Depts of Otolaryngology (JCS, KEM) and Biochemistry (MDW, JAP), The Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN.
- Note: Dr. Sniezek is now located at Tripler Army Medical Center, Honolulu, HI
Objective: Analyze p63 isoform expression on the RNA and protein level in normal, diseased, and malignant mucosa of the head and neck
Study Design: p63 isoform expression was analyzed in vivo in 36 head and neck squamous cell carcinoma (HNSCC) specimens and matched normal tissue controls. Further, p63 expression was evaluated in oral lichen planus, a benign mucosal lesion marked by hyperdifferentiation and apoptosis.
Methods: Immunohistochemistry, RT-PCR, and western analysis of p63 was performed on HNSCC specimens and matched normal tissue controls. p63 expression in oral lichen planus specimens was also examined by immunohistochemistry.
Results: RT-PCR analyses indicate that while all 3 DNp63 isoforms (a,b,g) are expressed in normal and malignant mucosa of the head and neck, DNp63a is the predominant transcript expressed. IHC analysis of 36 HNSCC specimens showed p63 expression in all tumors (36/36). Western analysis confirmed that DNp63a is the major isoform expressed at the protein level in tumors and normal tissue. In the pro-apoptotic condition of lichen planus, p63 is underexpressed by immunohistochemistry analysis.
Conclusion: While all 3 DNp63 isoforms are present in HNSCC, DNp63a protein is the predominant isoform expressed in HNSCC and is underexpressed in the pro-apoptotic condition of lichen planus. These findings support the hypothesis that p63 plays an anti-differentiation and anti-apoptotic role in the mnucosal epithelium of the head and neck, possibly leading to tumor formation.