Correlation of Somatostatin Receptor 1–5 Expression, [68Ga]Ga-DOTANOC, [18F]F-FDG PET/CT and Clinical Outcome in a Prospective Cohort of Pancreatic Neuroendocrine Neoplasms
by
,
Susanna Majala
1,2,*, 
Tiina Vesterinen
3,4,
Hanna Seppänen
5,
Harri Mustonen
5,
Jari Sundström
6,
Camilla Schalin-Jäntti
7,
Risto Gullichsen
1,
Jukka Schildt
8,
Jukka Kemppainen
2,9,
Johanna Arola
3,† and
Saila Kauhanen
1,2,† 1
Department of Surgery, Division of Digestive Surgery and Urology, Turku University Hospital, University of Turku, P.O. Box 52, FIN-20521 Turku, Finland
2
Turku PET Centre, Turku University Hospital, P.O. Box 52, FIN-20521 Turku, Finland
3
HUSLAB, HUS Diagnostic Center, Department of Pathology, Helsinki University Hospital, University of Helsinki, P.O. Box 400, FIN-00029 Helsinki, Finland
4
Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, P.O. Box 20, FIN-00014 Helsinki, Finland
5
Translational Cancer Medicine Research Program, Department of Surgery, Faculty of Medicine, Helsinki University Hospital, University of Helsinki, P.O. Box 340, FIN-00029 Helsinki, Finland
6
Department of Pathology, Turku University Hospital, P.O. Box 52, FIN-20521 Turku, Finland
7
Abdominal Center, Division of Endocrinology, Helsinki University Hospital, University of Helsinki, P.O. Box 340, FIN-00029 Helsinki, Finland
8
Department of Clinical Physiology and Nuclear Medicine, Helsinki University Hospital, Haartmaninkatu 4, P.O. Box 340, FIN-00029 Helsinki, Finland
9
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, P.O. Box 52, FIN-20521 Turku, Finland
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2022, 14(1), 162; https://doi.org/10.3390/cancers14010162
Submission received: 3 December 2021
/
Revised: 23 December 2021
/
Accepted: 26 December 2021
/
Published: 29 December 2021
(This article belongs to the Special Issue Current Status of Neuroendocrine Tumors with a Special Focus on Diagnosis and Novel Treatments)
Simple Summary
The need for prognostic and predictive biomarkers in pancreatic neuroendocrine neoplasms (PNENs) is great. Overexpression of somatostatin receptors (SSTRs) provides a molecular basis for imaging these tumors with 68Ga-labeled somatostatin (SST) PET/CT and for treatment with somatostatin analogs. We evaluated all 5 somatostatin receptors (SSTR1-5) with immunohistochemistry and prospectively compared the results with both [68Ga]Ga-DOTANOC and [18F]F-FDG PET/CT in a cohort of 21 non-functional (NF) PNENs. SSTR2 was the only SSTR subtype to correlate with [68Ga]Ga-DOTANOC PET/CT. High SSTR5 expression correlated with a low Ki-67 proliferation index, suggesting a better prognosis for these patients. Thus, our results confirm that SSTR2 has the highest impact on SSTR PET signaling of PNENs.
Abstract
Purpose: The aim of this study was to correlate immunohistochemical (IHC) tissue levels of SSTR1-5 with the receptor density generated from [68Ga]Ga-DOTANOC uptake in a prospective series of NF-PNENs. Methods: Twenty-one patients with a total of thirty-five NF-PNEN-lesions and twenty-one histologically confirmed lymph node metastases (LN+) were included in this prospective study. Twenty patients were operated on, and one underwent endoscopic ultrasonography and core-needle biopsy. PET/CT with both [68Ga]Ga-DOTANOC and [18F]F-FDG was performed on all patients. All histological samples were re-classified and IHC-stained with monoclonal SSTR1-5 antibodies and Ki-67 and correlated with [68Ga]Ga-DOTANOC and [18F]F-FDG PET/CT. Results: Expression of SSTR1-5 was detected in 74%, 91%, 80%, 14%, and 77% of NF-PNENs. There was a concordance of SSTR2 IHC with positive/negative [68Ga]Ga-DOTANOC finding (Spearman’s rho 0.382, p = 0.043). All [68Ga]Ga-DOTANOC-avid tumors expressed SSTR2 or SSTR3 or SSTR5. Expression of SSTR5 was higher in tumors with a low Ki-67 proliferation index (PI) (−0.353, 95% CI −0.654–0.039, p = 0.038). The mean Ki-67 PI for SSTR5 positive tumors was 2.44 (SD 2.56, CI 1.0–3.0) and 6.38 (SD 7.25, CI 2.25–8.75) for negative tumors. Conclusion: SSTR2 was the only SSTR subtype to correlate with [68Ga]Ga-DOTANOC PET/CT. Our prospective study confirms SSTR2 to be of the highest impact for SST PET/CT signal.
