Poster Presentation Advances in Neuroblastoma Research Congress 2016

Immunohistochemical evaluation of target expression in high-risk neuroblastoma samples to facilitate optimisation of molecular radiotherapy (#315)

Jennifer E Gains 1 , Neil J Sebire 2 , Veronica Moroz 3 , Alex Virasami 2 , Keith Wheatley 3 , Mark N Gaze 1
  1. University College London Hospitals NHS Foundation Trust, London, United Kingdom
  2. Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
  3. Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom

Introduction

Molecular radiotherapy targeting the noradrenaline transporter molecule (NAT) with 131I‑meta-iodobenylguanidine (mIBG) and the somatostatin receptor subtype-2 (SSTR-2) with 177Lu-DOTATATE are used for the treatment of relapsed and refractory neuroblastoma. Currently, patient selection for treatment is based on 123I-mIBG and 68Ga-DOTATATE imaging. This study aimed to quantify the degree and intensity of expression of both NAT and SSTR-2 in archival neuroblastoma tissue using immunohistochemistry and to correlate these with clinical factors.

Methods

Archived formalin fixed paraffin embedded neuroblastoma tissue was received from the Children’s Cancer and Leukaemia Group Tissue Bank. Each sample underwent immunohistochemistry for both NAT and SSTR-2 using commercially available monoclonal antibodies. Each sample was then scored for 1) intensity and 2) percentage of cells staining positively, for both NAT and SSTR2. Scores were correlated with known matched clinical data on age, stage, MYCN status and outcome. 

Results

75 tissue samples were available with matched clinical data at the time of analysis. The median age of the cohort studies was 18 months and 68% had INSS stage 4 disease. MYCN was amplified in 23%, not amplified in 61% and unknown in 16%. 83% of samples were poorly differentiated, 14% were differentiating and 4% were undifferentiated. There was considerable heterogeneity of expression of NAT and SSTR-2 amongst the samples. In stage 4 patients, 56% had high intensity and 47% high percentage expression of SSTR-2 whereas 8% had high intensity and 39% high percentage expression of NAT.

Conclusion

Immunohistochemistry may possibly be used to facilitate the appropriate selection of molecular radiotherapy in neuroblastoma. Immunohistochemical assessment of target expression will be correlated with results of nuclear imaging in a current trial of molecular radiotherapy in neuroblastoma. These results suggest that molecular radiotherapy targeting both NAT and SSTR2 simultaneously or sequentially may have clinical advantages.