Abstract
Simple SummaryThe 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.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.
Highlights
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) exhibit heterogeneous phenotypes with a variable clinical course ranging from very indolent tumors to highly aggressive carcinomas
Our group previously showed that dual tracer imaging with [68Ga]Ga-DOTANOC and [18F]F-FDG can predict the proliferation index, the aggressiveness of NF-Pancreatic neuroendocrine neoplasms (PNENs) [8]
Dsectoariles oofft4h,e 1m3emtubmraonrosush,acdytoapKlasrmenicn, ianngd score o o5opvni=melry0maTl.hl0tuhee4nrxe3oeph)twr.iuesastmsosicnoohonrecmowofriScirteaShllTaeRtaxio1pK-nr5erb,seaestsniwodnneei.esnnTcgrh[i6bes8recGedoawri]nGeasatoh-nDfeoO2mcToedArtihrNdeolOdantsCioostPencEebtTxieo/ptnwCr, eTeaesraensnsSdShSSSoTTSwRTRn1R2oi1nr(oSFSriSpSgTSeuRTare3Rr-m345-. an’s rh expression profile and NETPET score or between SSTR1 or SSTR3-5 expression profile a3n.2d.KSrSenTnRin1g, 3sc,o4r,e.5ImExmpurneoshsiostnocDheomesicNaloStSCTRor1r-5elmateemwbirtahne[6e8Gxpar]eGssaio-Dn pOroTfiAleNs vOeCrsuPsET/CT [68Ga]OGav-eDrOaTllA, NexOpCreuspstiaokne ooffaSllStuTmRo1r,sSaSreTpRr3es,eSnSteTdRin4,FaignudreS5SaT–eR. 5 were detected in 74 14%, and 77% of NF-PNENs, respectively
Summary
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) exhibit heterogeneous phenotypes with a variable clinical course ranging from very indolent tumors to highly aggressive carcinomas. Pancreatic neuroendocrine neoplasms (PNENs) have the lowest five-year survival rate (23%) of all GEP-NEN sites [1]. The 2017 update of the WHO classification incorporates a new subcategory of pancreatic neuroendocrine tumor grade 3 (PNET G3) into the well-differentiated NEN category [3]. Preoperative histopathological evaluation is often problematic, non-invasive diagnostic imaging with [18F]F-FDG-PET/CT helps to predict the tumor grade better [5,6,7,8]. Our group previously showed that dual tracer imaging with [68Ga]Ga-DOTANOC and [18F]F-FDG can predict the proliferation index, the aggressiveness of NF-PNENs [8]
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