Analysis of somatostatin receptor 2A immunohistochemistry, RT-qPCR, and in vivo PET/CT data in patients with pancreatic neuroendocrine neoplasm

Pancreas. 2015 May;44(4):648-54. doi: 10.1097/MPA.0000000000000316.

Abstract

Objective: Gallium 68 somatostatin receptor (SSTR) positron emission tomography/computed tomography (PET/CT) is one of the most sensitive imaging methods for pancreatic neuroendocrine tumors. The aim of the study was to correlate the receptor density generated from the static PET/CT (maximum standard uptake values [SUVmax], mean standard uptake values [SUVmean]) with subtype 2A SSTR (SSTR2A) immunohistochemistry and reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) gene-expression data.

Methods: Thirty-nine tumor specimens (17 primary pancreatic tumors [PTs], 22 metastases [MTS]) of 19 patients with PET/CT scans preoperatively were evaluated. Subtype 2A SSTR expression was quantified immunohistochemically (immunoreactive score [IRS]) and on messenger RNA (mRNA) level by RT-qPCR.

Results: The PT and MTS did not differ significantly in their SUVmax (P = 0.07) but displayed a dissimilarity with respect to their SSTR2A expression (mean [SD] IRS PT, 8.8 [3.6] vs mean [SD] IRS MTS, 5.1 [4.5]; P = 0.02).The SUVmean was highly significantly correlated to SSTR2A mRNA expression (C = 0.85, P < 0.001) and moderately to SSTR2A protein expression (C = 0.53, P = 0.05). Moreover, the SUVmax correlated moderately with SSTR2A protein expression (C = 0.44, P = 0.03) and mRNA expression (C = 0.64, P = 0.042).

Conclusions: The SUVmax and SUVmean are reliable ex vivo parameters for in vivo quantification of SSTR expression in pancreatic neuroendocrine tumors. Both immunohistochemistry and RT-qPCR are comparable methods for SSTR2A quantification. The PT and MTS differ significantly in their SSTR2A expression. This fact should be taken into account when treating patients with somatostatin analogs or peptide receptor radionuclide therapy.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Female
  • Gallium Radioisotopes
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Multimodal Imaging*
  • Neoplasm Metastasis
  • Neuroendocrine Tumors / diagnosis*
  • Neuroendocrine Tumors / metabolism
  • Neuroendocrine Tumors / pathology
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Positron-Emission Tomography*
  • Radiopharmaceuticals
  • Real-Time Polymerase Chain Reaction
  • Receptors, Somatostatin / metabolism*
  • Retrospective Studies
  • Tomography, X-Ray Computed*

Substances

  • Biomarkers, Tumor
  • Gallium Radioisotopes
  • Radiopharmaceuticals
  • Receptors, Somatostatin
  • SSTR2 protein, human