Survivin expression in juvenile-onset recurrent respiratory papillomatosis

Recurrent respiratory papillomatosis (RRP), caused by the human papillomavirus, is characterized by unregulated growth of wartlike neoplasms on laryngeal mucosa. Apoptosis is important in normal cellular homeostasis, and dysregulation of this process is thought to govern the behavior of certain neoplasms. This study evaluates the expression of several pro-apoptotic and anti-apoptotic factors in papillomas of patients with RRP, with a specific interest in survivin, a cell cycle-regulated anti-apoptotic factor. Three antiapoptotic and 6 pro-apoptotic messenger RNA (mRNA) species were quantified by ribonuclease protection assay in 11 RRP papilloma specimens and 5 normal laryngeal specimens. Anti-apoptotic and pro-apoptotic mRNA ratios were quantified by normalizing to the ribosomal protein L32 and compared between specimens. Protein expression of survivin in tissue samples was also evaluated. The mean (±SD) expression of survivin was almost fivefold greater in the RRP papillomas than in normal tissue (14.2% ± 2.5% versus 3.0% ± 0.8% of L32, p =.003). The RRP specimens also had greater expression of XIAP, Fas, and p53 than did the normal tissue. Survivin protein was differentially expressed in the papilloma specimens, and was greatest in a papilloma that underwent malignant transformation. Survivin was absent in all normal laryngeal tissue tested. Apoptotic factors in general appear to be up-regulated in papillomatous tissue as compared to normal laryngeal tissue and may suggest a higher proliferation rate and cell turnover. Survivin is abundant in papillomas and absent in normal laryngeal tissue. Dysregulation of apoptosis as determined by abnormal expression of anti-apoptotic factors like survivin and XIAP probably favors papilloma growth and survival. Such factors may represent potential targets in the treatment of this disease.