Liver, Pancreas and Biliary TractLesion-by-lesion correlation between uptake at FDG PET and the Ki67 proliferation index in resected pancreatic neuroendocrine tumors
Introduction
Pancreatic neuroendocrine neoplasms are classified depending on the pathological assessment of differentiation and tumor pathological grade (G), which is determined by the Ki67 proliferation index [1]. The 2017 WHO classification distinguishes well-differentiated G1, G2 and G3 pancreatic neuroendocrine tumors (PanNET) from poorly-differentiated G3 pancreatic neuroendocrine carcinomas [1]. This classification is of paramount importance for prognostic evaluation and therapeutic management. Nevertheless, the evaluation of Ki67 is subject to heterogeneity due to sampling bias, inter- and intra-tumor heterogeneity [[2], [3], [4]].
Tumor uptake on 18fluorodeoxyglucose (FDG) positron-emitting tomography (PET) may be relevant for the prognostic evaluation of PanNET. Higher tumor uptake, evaluated by the tumor maximal standardized uptake value (SUVmax) or the tumor-to-liver SUVmax ratio (SUVmax T/L), seems correlated to increased Ki67 and worse prognosis [[5], [6], [7], [8], [9]]. Accordingly, the diagnostic sensitivity of FDG-PET is higher for PanNET with Ki67 ≥ 10% [6,10]. The intensity of FDG-PET uptake was reported to be a better prognostic tool than Ki67 [8,10]. Especially, Ezziddin et al. [8] reported that a metabolic grading system ([mG], mG1, SUVmax T/L < 1; mG2, SUVmax T/L 1–2.3; mG3, SUVmax T/L > 2.3) was more discriminant for prognosis than the pathological grade.
However, these studies compared SUVmax (tumor pixel of highest uptake) determined on whole-body FDG-PET, with the Ki67 of the most easily accessible lesion that was generally sampled a long time ago and was not necessarily the lesion with highest uptake, leading to potential discrepancies. To better assess this relationship, we performed a lesion-by-lesion correlation between the preoperative SUVmax T/L ratio (and mG) and the Ki67 index (and the pathological grade) analyzed on surgically resected specimens of PanNET.
Section snippets
Patients
A retrospective analysis of consecutive patients operated on (primary tumor and/or metastases) for a pathologically proven sporadic or hereditary well-differentiated PanNET, between October 2010 and February 2018, was conducted at a tertiary center with expertise in neuroendocrine tumors. Patients were included if they had performed an FDG-PET within the 6 months prior to surgery. Surgery was always decided in NET-dedicated multidisciplinary board. Patients were excluded if they had
Patients
Twenty-one patients (male gender 62%) with a median age of 49.9 years, were operated on for PanNET and/or associated metastases (Table 1). Four patients had a functioning syndrome (one VIPoma, one glucagonoma, one gastrinoma and one parathormone-related syndrome). One patient had genetic predisposition (von Hippel–Lindau syndrome). No patient had received antitumor treatment with neoadjuvant purpose. Two patients had received previous somatostatin analogs (the patient with VIPoma and the one
Discussion
Our study confirms the correlation between Ki67 and tumor uptake at FDG-PET [8]. Preoperative mG was significantly associated with the pathological grade assessed on the resected specimen. Especially, all lesions but one with low FDG uptake (mG1) were G1 or G2, and all lesions with strong FDG uptake (mG3) were G3 or G2 with Ki67 > 10% (excepted one G2 lesion).
Previous studies suggested gross correlation between FDG uptake and tumor grade [[5], [6], [7], [8], [9], [10]]. However, in these
Conflict of interest
None declared.
Acknowledgments
The authors did not receive any financial support for this work.
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