Immunohistochemical evaluation of molecular radiotherapy target expression in neuroblastoma tissue

Jennifer E. Gains, Neil J. Sebire, Veronica Moroz, Keith Wheatley, Mark N. Gaze

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)
153 Downloads (Pure)

Abstract

PURPOSE: Neuroblastoma may be treated with molecular radiotherapy, (131)I meta-Iodobenzylguanidine and (177)Lu 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.

Original languageEnglish
Pages (from-to)402-411
JournalEuropean Journal Nuclear Medicine Molecular Imaging
Volume45
Issue number3
Early online date17 Oct 2017
DOIs
Publication statusPublished - 1 Mar 2018

Keywords

  • Journal Article
  • immunohistochemistry
  • lutetium DOTATATE
  • meta-iodobenzylguanidine
  • molecular radiotherapy
  • neuroblastoma
  • noradrenalin transporter molecule
  • somatostatin receptor

Fingerprint

Dive into the research topics of 'Immunohistochemical evaluation of molecular radiotherapy target expression in neuroblastoma tissue'. Together they form a unique fingerprint.

Cite this