Somatostatin receptor activity assessed by 68Ga-DOTATOC PET can preoperatively predict DAXX/ATRX loss of expression in well-differentiated pancreatic neuroendocrine tumors.

Abstract

PURPOSE:

To evaluate the role of 68Ga-DOTATOC PET parameters in predicting DAXX/ATRX loss of expression in patients with Pancreatic neuroendocrine tumors (PanNET) candidate to surgery.

METHODS:

This retrospective study included 72 consecutive patients with PanNET (January 2018-March 2022) who underwent to 68Ga-DOTATOC PET for preoperative staging. Image analysis: qualitative assessment and extraction of SUVmax, SUV mean, somatostatin receptor density (SRD), and total lesion somatostatin receptor density (TLSRD) from primary PanNET. Radiological diameter and biopsy information (grade, Ki67) were collected. Loss of expression (LoE) of DAXX/ATRX was assessed by immunohistochemistry on surgical specimen. Student t-test, univariate and multivariate logistic regression and ROC curves have been used to investigate the predictive value of PET parameters on DAXX/ATRX LoE.

RESULTS:

Forty-two/72 patients had a G1, 28/72 a G2, and 2/72 a G3 PanNET. Seven/72 patients had DAXX LoE, 10/72 ATRX LoE, and 2/72 DAXX/ATRX LoE. SRD and TLSRD could predict DAXX LoE (p = 0.002, p = 0.018, respectively). By evaluating SRD in combination with radiological diameter, only SRD maintained statistical significance (multivariate logistic regression: p = 0.020, OR = 1.05), providing the best prediction (AUC-ROC = 79.01%; cut-off = 46.96; sensitivity = 77.78%; specificity = 88.89%). In the sub-analysis performed on 55 patients with biopsy availability, SRD demonstrated its role in providing useful and additional information (multivariate logistic regression: SRD p = 0.007; grade p = 0.040).

CONCLUSION:

SRD has a predictive role on DAXX LoE in PanNETs, with higher probability of LoE at increasing SRD values. SRD provides complementary/additional information to grade assessed on biopsy material, and the combined use of these approaches might support patients' management by preoperatively identifying subjects with more aggressive diseases.

• Authors: Paola Mapelli, Carolina Bezzi, Francesca Muffatti, Samuele Ghezzo, Francesco Baldassi, Marco Schiavo Lena, Valentina Andreasi, Carla Canevari, Patrizia Magnani, Francesco De Cobelli, Luigi Gianolli, Stefano Partelli, Massimo Falconi, Maria Picchio
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 50 Issue 9 Pg. 2818-2829 (07 2023) ISSN: 1619-7089 [Electronic] Germany
• PMID: 37010579 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Edotreotide
• X-linked Nuclear Protein
• Receptors, Somatostatin
• Gallium Radioisotopes
• Adaptor Proteins, Signal Transducing
• ATRX protein, human
• DAXX protein, human
• Molecular Chaperones
• Co-Repressor Proteins

Topics

• Humans
• Neuroendocrine Tumors (metabolism)
• X-linked Nuclear Protein (metabolism)
• Receptors, Somatostatin (metabolism)
• Gallium Radioisotopes
• Retrospective Studies
• Adaptor Proteins, Signal Transducing (analysis, metabolism)
• Pancreatic Neoplasms (metabolism)
• Positron-Emission Tomography
• Molecular Chaperones (metabolism)
• Co-Repressor Proteins (metabolism)