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

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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.

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Acknowledgements

This work has been partly supported by an AIRC Regional grant 2009 (assigned to M.R.). The authors are grateful to Vincenza Guzzardo, Mariangela Balistreri, Vanni Lazzarin, and Cristiano Lanza for their technical assistance.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Medical Diagnostic Sciences & Special Therapies, Surgical Pathology & Cytopathology Unit, University of Padua-Italy, Padua, Italy

    Matteo Fassan, Marco Pizzi, Claudia Mescoli, Kathrin Ludwig & Massimo Rugge

  2. Surgical Pathology & Cytopathology Unit, Azienda Ospedaliera di Padova, Padua, Italy

    Luciano Giacomelli & Massimo Rugge

  3. Department of Oncological and Surgical Sciences, Clinica Chirurgica II, University of Padua-Italy, Padua, Italy

    Salvatore Pucciarelli

  4. Surgical Pathology Unit, Istituto Oncologico Veneto–IOV-IRCCS, Via Aristide Gabelli, 61, Padua, 35121, Italy

    Massimo Rugge

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  1. Matteo Fassan
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  2. Marco Pizzi
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  3. Luciano Giacomelli
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  4. Claudia Mescoli
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  5. Kathrin Ludwig
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  6. Salvatore Pucciarelli
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  7. Massimo Rugge
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Correspondence to Massimo Rugge.

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Fassan, M., Pizzi, M., Giacomelli, L. et al. PDCD4 nuclear loss inversely correlates with miR-21 levels in colon carcinogenesis. Virchows Arch 458, 413–419 (2011). https://doi.org/10.1007/s00428-011-1046-5

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  • DOI: https://doi.org/10.1007/s00428-011-1046-5

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