Programmed cell death 4 (PDCD4) has recently been demonstrated to be a new tumor 
suppressor gene involved in colon carcinogenesis. PDCD4 immunohistochemical 
expression was assessed in 300 polypoid lesions of the colon mucosa (50 
hyperplastic polyps [HP], 50 serrated adenomas [SA], 50 tubular adenomas with 
low-grade-intraepithelial neoplasia [LG-IEN], 50 tubular adenomas with 
high-grade-IEN [HG-IEN]), and in 50 colon adenocarcinomas (CRC). As normal 
controls, we considered 50 biopsy samples obtained from patients with irritable 
bowel syndrome (N). We further investigated PDCD4 messenger RNA (mRNA) levels by 
quantitative real-time polymerase chain reaction (PCR) in a different series of 
N, LG-IEN, HG-IEN, and CRC biopsy samples. miR-21 expression (an important 
PDCD4-expression regulator) was also determined by quantitative real-time PCR 
and in situ hybridization. Normal colocytes and HP featured strong PDCD4 nuclear 
immunostaining whereas a significantly lower PDCD4 nuclear expression was 
observed in dysplasia (low- and high-grade adenomas and SA) and invasive CRC. 
PDCD4 immunostaining and mRNA levels decreased significantly as the phenotypic 
changes occurring during colon carcinogenesis progressively increased 
(p < 0.001). As expected, miR-21 expression was significantly upregulated in 
preneoplastic/neoplastic samples, consistent with PDCD4 downregulation. These 
results consistently support the use of nuclear PDCD4 immunohistochemical 
downregulation as a novel biomarker for the diagnosis of dysplastic/neoplastic 
lesions in colon biopsy samples.