Clinical significance of programmed cell death 4 expression in malignant progression of human nasal inverted papillomas.

Programmed cell death 4 (PDCD4) is a novel tumor suppressor gene that can inhibit tumor neoplastic transformation and progression in cultured cells and gene knock-out mouse models. Lost or decreased PDCD4 expression has been associated with progression and prognosis of multiple types of human tumors. However, the expression and clinical significance of PDCD4 in nasal inverted papillomas (NIPs) has not been investigated. We compared PDCD4 expression in 64 samples of NIPs, 23 of associated squamous cell carcinomas (SCCs), and 19 normal nasal samples at mRNA and protein levels by RT-PCR, western blot analysis, and immunohistochemistry. PDCD4 mRNA expression was reduced in 52% of NIP frozen samples (13/25), and the protein level was diminished in 56.3% of samples (36/64) as compared with 19 normal nasal samples, which expressed high levels of PDCD4 mRNA and protein. Furthermore, altered expression of PDCD4 was associated with the clinicopathological features Krouse stage and dysplasia. Importantly, we found a strong negative correlation of PDCD4 expression and Ki-67 labeling index in NIPs (r=-0.6645, p<0.001). In addition, the 3 tissue-sample groups significantly differed in PDCD4 expression and Ki-67 labeling index. Thus, PDCD4 expression may play a key role in pre-cancerous lesions of human NIPs and may help predict malignant progression from benign nasal tumors to associated SCC.