Grading of Neuroendocrine Carcinomas: Correlation of 68Ga-PET/CT Scan with Tissue Biomarkers

Dis Markers. 2018 Dec 2;2018:6878409. doi: 10.1155/2018/6878409. eCollection 2018.


There is a growing need for more accurate biomarkers to facilitate the diagnosis and prognosis of patients with grade (G) 3 neuroendocrine carcinomas (NECs). In particular, the discrimination between well-differentiated neuroendocrine carcinomas (WD-NECs) and poorly differentiated neuroendocrine carcinomas (PD-NECs) is still an unmet need. We previously showed that 68Gallium-(68Ga-) PET/CT positivity is a prognostic factor in patients with gastroenteropancreatic (GEP) G3 NECs, correlating with a better outcome in terms of overall survival. Here, we hypothesize that 68Ga-PET/CT could help to discriminate between WD-NECs and PD-NECs, adding complementary information to that obtained from morphologic and biologic factors. A retrospective, single-institution study was performed on 11 patients with histologically confirmed, measurable G3 large- or small-cell GEP-NECs according to the 2017 WHO classification. The staging procedures included a 68Ga-PET/CT scan. Results of 68Ga-PET/CT were correlated in univariate analysis with loss of tissue immunohistochemical expression of DAXX/ATRX or RB1 frequently associated with WD-NECs or PD-NECs, respectively. None of the patients with positive 68Ga-PET/CT showed loss of RB1 expression, whereas among those (n = 6) with negative 68Ga-PET/CT, 4 showed loss of expression. A trend towards a correlation between loss of RB1 expression and negative 68Ga-PET/CT was observed. Our preliminary data support the hypothesis that PD-NECs carrying RB1 mutation and loss of its expression may be associated with negative 68Ga-PET/CT. If confirmed in a larger clinical trial, 68Ga-PET/CT would help in the stratification of G3 NECs.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Neuroendocrine / diagnostic imaging*
  • Carcinoma, Neuroendocrine / pathology*
  • Co-Repressor Proteins
  • Down-Regulation
  • Female
  • Gallium Radioisotopes / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • Molecular Chaperones
  • Mutation
  • Neoplasm Grading
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Positron Emission Tomography Computed Tomography / methods*
  • Retinoblastoma Binding Proteins / genetics
  • Retinoblastoma Binding Proteins / metabolism
  • Retrospective Studies
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • X-linked Nuclear Protein / genetics
  • X-linked Nuclear Protein / metabolism


  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • Co-Repressor Proteins
  • DAXX protein, human
  • Gallium Radioisotopes
  • Molecular Chaperones
  • Nuclear Proteins
  • RB1 protein, human
  • Retinoblastoma Binding Proteins
  • Ubiquitin-Protein Ligases
  • ATRX protein, human
  • X-linked Nuclear Protein