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Immunohistochemical evaluation of molecular radiotherapy target expression in neuroblastoma tissue

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Abstract

Purpose

Neuroblastoma may be treated with molecular radiotherapy, 131I meta-Iodobenzylguanidine and 177Lu Lutetium DOTATATE, directed at distinct molecular targets: Noradrenaline Transporter Molecule (NAT) and Somatostatin Receptor (SSTR2), respectively. This study used immunohistochemistry to evaluate target expression in archival neuroblastoma tissue, to determine whether it might facilitate clinical use of molecular radiotherapy.

Methods

Tissue bank samples of formalin fixed paraffin embedded neuroblastoma tissue from patients for whom clinical outcome data were available were sectioned and stained with haematoxylin and eosin, and monoclonal antibodies directed against NAT and SSTR2. Sections were examined blinded to clinical information and scored for the percentage and intensity of tumour cells stained. These data were analysed in conjunction with clinical data.

Results

Tissue from 75 patients was examined. Target expression scores varied widely between patients: NAT median 45%, inter-quartile range 25% - 65%; and SSTR2 median 55%, interquartile range 30% – 80%; and in some cases heterogeneity of expression between different parts of a tumour was observed. A weak positive correlation was observed between the expression scores of the different targets: correlation coefficient = 0.23, p = 0.05. MYCN amplified tumours had lower SSTR2 scores: mean difference 23% confidence interval 8% - 39%, p < 0.01. Survival did not differ by scores.

Conclusions

As expression of both targets is variable and heterogeneous, imaging assessment of both may yield more clinical information than either alone. The clinical value of immunohistochemical assessment of target expression requires prospective evaluation. Variable target expression within a patient may contribute to treatment failure.

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Funding

This work was made possible by a generous grant from the Adam Hay Fund of the Children’s Cancer and Leukaemia Group. The Children’s Cancer and Leukaemia Group Tissue Bank is funded by Cancer Research UK. The authors were supported by: the National Institute for Health Research University College London Hospitals Biomedical Research Centre, The Neuroblastoma Alliance and Joining Against Cancer in Kids. The Cancer Research UK Clinical Trials Unit at the University of Birmingham receives core funding from Cancer Research UK.

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Authors and Affiliations

  1. Department of Oncology, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London, NW1 2PG, UK

    Jennifer E. Gains & Mark N. Gaze

  2. Department of Pathology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH, UK

    Neil J. Sebire

  3. Cancer Research UK Clinical Trials Unit, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

    Veronica Moroz & Keith Wheatley

Authors
  1. Jennifer E. Gains
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  2. Neil J. Sebire
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  3. Veronica Moroz
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  4. Keith Wheatley
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  5. Mark N. Gaze
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Corresponding author

Correspondence to Mark N. Gaze.

Ethics declarations

Conflict of interest

All authors declare that they have no conflicts of interest as follows:

Jennifer E. Gains declares that she has no conflict of interest.

Neil J. Sebire declares that he has no conflict of interest.

Veronica Moroz declares that she has no conflict of interest.

Keith Wheatley declares that he has no conflict of interest.

Mark N. Gaze declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with animals performed by any of the authors.

This article does not contain any studies with human participants performed by any of the authors.

This article does contain a study on human tissue obtained from the Children’s Cancer and Leukaemia Group Tissue Bank. All tissue banking procedures are performed in accordance with the ethical standards of the national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study, or their parent or guardian, prior to tissue banking. This consent also prospectively covered subsequently approved studies on the tissue.

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Gains, J.E., Sebire, N.J., Moroz, V. et al. Immunohistochemical evaluation of molecular radiotherapy target expression in neuroblastoma tissue. Eur J Nucl Med Mol Imaging 45, 402–411 (2018). https://doi.org/10.1007/s00259-017-3856-4

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  • DOI: https://doi.org/10.1007/s00259-017-3856-4

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