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Immunohistochemical evaluation of molecular radiotherapy target expression in neuroblastoma tissue

Gains, JE; Sebire, NJ; Moroz, V; Wheatley, K; Gaze, MN; (2018) Immunohistochemical evaluation of molecular radiotherapy target expression in neuroblastoma tissue. European Journal of Nuclear Medicine and Molecular Imaging , 45 (3) pp. 402-411. 10.1007/s00259-017-3856-4. Green open access

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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.

Type: Article
Title: Immunohistochemical evaluation of molecular radiotherapy target expression in neuroblastoma tissue
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s00259-017-3856-4
Publisher version: https://doi.org/10.1007/s00259-017-3856-4
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Immunohistochemistry, Lutetium DOTATATE, meta-Iodobenzylguanidine, Molecular Radiotherapy, Neuroblastoma, Noradrenalin Transporter Molecule, Somatostatin Receptor
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Population, Policy and Practice Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10080731
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