Virchows Archiv

, Volume 458, Issue 4, pp 413–419

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

  • Matteo Fassan
  • Marco Pizzi
  • Luciano Giacomelli
  • Claudia Mescoli
  • Kathrin Ludwig
  • Salvatore Pucciarelli
  • Massimo Rugge
Original Article

DOI: 10.1007/s00428-011-1046-5

Cite this article as:
Fassan, M., Pizzi, M., Giacomelli, L. et al. Virchows Arch (2011) 458: 413. doi:10.1007/s00428-011-1046-5

Abstract

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.

Keywords

PDCD4miR-21Tumor suppressor geneColon biopsyColon cancer

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Matteo Fassan
    • 1
  • Marco Pizzi
    • 1
  • Luciano Giacomelli
    • 2
  • Claudia Mescoli
    • 1
  • Kathrin Ludwig
    • 1
  • Salvatore Pucciarelli
    • 3
  • Massimo Rugge
    • 1
    • 2
    • 4
  1. 1.Department of Medical Diagnostic Sciences & Special Therapies, Surgical Pathology & Cytopathology UnitUniversity of Padua-ItalyPaduaItaly
  2. 2.Surgical Pathology & Cytopathology UnitAzienda Ospedaliera di PadovaPaduaItaly
  3. 3.Department of Oncological and Surgical Sciences, Clinica Chirurgica IIUniversity of Padua-ItalyPaduaItaly
  4. 4.Surgical Pathology UnitIstituto Oncologico Veneto–IOV-IRCCSPaduaItaly