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Prevalence and Clinical Correlations of Somatostatin Receptor-2 (SSTR2) Expression in Neuroblastoma

Natasha Alexander1,2, Paula Marrano3, Paul Thorner3,4

  • 1Departments of Pediatrics, Division of Hematology/Oncology.

Journal of Pediatric Hematology/Oncology
|October 19, 2018
PubMed

Insights

Neuroblastoma (NB) cells express somatostatin receptors (SSTRs), particularly SSTR2. This study found SSTR2 expression in NB tumors, suggesting potential for targeted peptide therapies in relapsed or refractory neuroblastoma.

Area of Science:

  • Pediatric Oncology
  • Nuclear Medicine
  • Molecular Imaging

Background:

  • Relapsed neuroblastoma (NB) poses treatment challenges, especially for patients unresponsive to I-metaiodobenzylguanidine (MIBG) therapy.
  • Targeted therapies using radiolabeled agents are being explored for these difficult-to-treat cases.
  • Somatostatin receptors (SSTRs), particularly SSTR2, are expressed on NB cells and are targets for agents like (DOTA-Tyr)-octreotate.

Purpose of the Study:

  • To investigate somatostatin receptor subtype 2 (SSTR2) expression in neuroblastoma (NB) tumors.
  • To correlate SSTR2 levels with clinical features, norepinephrine transporter (NET) expression, and MIBG avidity.
  • To assess the potential of SSTR2-targeted agents for NB patients, including those with relapsed or refractory disease.

Main Methods:

  • Immunohistochemistry was used to quantify SSTR2 and NET expression scores (0-3) in NB tumor biopsies from 69 patients (36 high-risk, 33 non-high-risk).
  • Digital image analysis assessed staining intensity and distribution for SSTR2 and NET.
  • Statistical analysis correlated SSTR2 scores with clinical data (age, stage, MYCN amplification, histology), MIBG avidity, and NET expression.

Main Results:

  • The median SSTR2 score across 69 patients was 1.31.
  • Non-high-risk NB showed significantly higher SSTR2 scores compared to high-risk NB (P=0.032).
  • Higher SSTR2 expression was observed in MIBG-avid tumors compared to MIBG-nonavid tumors.
  • SSTR2 expression did not correlate with age, INSS stage, MYCN amplification, or histology.
  • SSTR2 scores were not significantly associated with NET scores (r=-0.062, P=0.62).
  • Patients with relapsed or progressive disease (n=26) had a median SSTR2 score of 1.33.

Conclusions:

  • Neuroblastoma tumors, including those in relapsed or progressive disease, express SSTR2 at diagnosis.
  • SSTR2 expression suggests that patients with NB may be suitable candidates for targeted imaging or therapy with radiolabeled DOTA-conjugated peptides.
  • These findings support the investigation of alternative targeted agents for neuroblastoma management, particularly in MIBG-refractory cases.

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