PDCD4 nuclear loss inversely correlates with miR-21 levels in colon carcinogenesis

Virchows Arch. 2011 Apr;458(4):413-9. doi: 10.1007/s00428-011-1046-5. Epub 2011 Jan 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adenoma / genetics
  • Adenoma / metabolism
  • Adenoma / pathology
  • Adenomatous Polyps / genetics
  • Adenomatous Polyps / metabolism
  • Adenomatous Polyps / pathology
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Biomarkers, Tumor / analysis
  • Carcinoma in Situ / genetics
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / pathology
  • Cell Nucleus / metabolism*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Gene Expression
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / analysis
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction


  • Apoptosis Regulatory Proteins
  • Biomarkers, Tumor
  • MIRN21 microRNA, human
  • MicroRNAs
  • PDCD4 protein, human
  • RNA, Messenger
  • RNA-Binding Proteins