Inflammatory bowel diseases (IBDs; both ulcerative colitis [UC] and Crohn's 
colitis [CC]) are well-established predisposing pathological conditions for 
colorectal cancer (CRC) development. In IBDs, both the endoscopy and the 
histology assessment of CRC precursors (i.e., dysplasia, also defined as 
intraepithelial neoplasia) are associated with low interobserver consistency, 
and no reliable dysplasia-specific biomarker is available. The programmed cell 
death 4 (PDCD4) tumor suppressor gene is involved in sporadic colorectal 
oncogenesis, but scanty information is available on its involvement in 
IBD-associated colorectal oncogenesis. One hundred twenty tissue samples 
representative of active and inactive IBD and of flat dysplasia were obtained 
from 30 cases of UC and 30 of CC who undergone colectomy. Twenty additional 
biopsy samples obtained from patients with irritable bowel syndrome acted as 
normal controls. PDCD4 expression was assessed by immunohistochemistry; the 
expression of miR-21 (a major PDCD4 regulator) was investigated by quantitative 
real-time PCR and in situ hybridization in different series of a hundred 
samples. Tissue specimens from both controls and inactive IBD consistently 
featured strong PDCD4 nuclear immunostain; conversely, lower PDCD4 nuclear 
expression was featured by both active IBD and IBD-associated dysplastic 
lesions. Significant PDCD4 down-regulation distinguished IBD-associated 
dysplasia (p < 0.001) versus active IBD. In both active IBD and dysplasia, PDCD4 
down-regulation was significantly associated with miR-21 up-regulation. PDCD4 
nuclear down-regulation (which parallels miR-21 up-regulation) is involved in 
the molecular pathway of IBD-associated carcinogenesis. PDCD4 nuclear expression 
may be usefully applied as ancillary maker in the histological assessment of 
IBD-associated dysplastic lesions.