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High levels of polo-like kinase 1 and phosphorylated translationally controlled tumor protein indicate poor prognosis in neuroblastomas

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Abstract

Despite multimodality treatment, the long-term survival of high-risk patients with neuroblastomas is below 50 %. New anti-mitotic drugs against targets, such as polo-like kinase 1 (PLK1), are being evaluated in early phase clinical trials. PLK1 phosphorylates the translationally controlled tumor protein (TCTP). We investigated the expression of PLK1 and the phosphorylated substrate, pTCTP, by immunostaining eighty-eight neuroblastomas. Digitally scanned slides were scored using image analysis software. The median PLK1 and pTCTP proliferation indices (PIs) were 4.6 and 1 % respectively. There was moderate positive correlation between PLK1 and pTCTP (ρ = 0.65). The PIs for both markers were significantly higher in neuroblastomas from patients with adverse clinical (advanced-stage, high-risk group, primary abdominal compared to extra-abdominal sites), biological (MYCN amplification, 1p deletion, 17q gain) and pathological (undifferentiated or poorly differentiated status, high mitosis-karyorrhexis index, [MKI], unfavorable histology) factors. Using Cox regression models, higher-than-median PLK1 and pTCTP PIs were associated with a shorter overall survival (OS) and event-free survival (EFS) in the univariate analyses. In the multivariate analyses, a high PLK1 PI count was associated with significantly shorter OS and EFS, independent of MYCN amplification and MKI; in addition, the significantly shorter EFS was independent of the risk-group. After adjustment for MKI and MYCN amplification, and for risk-group, high pTCTP PI was also associated with significantly shorter OS. Our study shows that PLK1 provides valuable prognostic information in patients with neuroblastomas.

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Acknowledgments

The authors are grateful to Mike Luckett for technical advice. The authors also acknowledge the clinicians, radiologists and all the individuals who were involved in the management of the patients.

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Authors and Affiliations

  1. School of Cellular and Molecular Medicine, University of Bristol, School of Medical Sciences, University Walk, Bristol, BS8 1TD, UK

    Pramila Ramani

  2. Department of Histopathology, University Hospitals Bristol NHS Foundation Trust, Bristol Royal Infirmary, Bristol, BS2 8HW, UK

    Pramila Ramani & Emile Sowa-Avugrah

  3. Clinical Trials and Evaluation Unit, University of Bristol, School of Clinical Sciences, Bristol Royal Infirmary, Bristol, BS2 8HW, UK

    Rachel Nash & Chris Rogers

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  1. Pramila Ramani
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  2. Rachel Nash
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Correspondence to Pramila Ramani.

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Ramani, P., Nash, R., Sowa-Avugrah, E. et al. High levels of polo-like kinase 1 and phosphorylated translationally controlled tumor protein indicate poor prognosis in neuroblastomas. J Neurooncol 125, 103–111 (2015). https://doi.org/10.1007/s11060-015-1900-4

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  • DOI: https://doi.org/10.1007/s11060-015-1900-4

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