Metabolomic characteristics of solid pseudopapillary tumor of the pancreas : relationship with high intensity 18F-FDG PET-scan

Abstract

Introduction: Solid pseudopapillary tumor (SPT) of the pancreas is a very rare pathologic condition occurring predominantly in female patients. Surgical resection is only way to cure of the disease, but the origin of the tumor and natural course of the disease are still unknown. Recently, 18F-FDG PET / PET-CT scan has been widely applied for differential diagnosis, preoperative staging, and determining treatment effect. Only a few literatures investigated the appearances of SPTs on 18F-FDG PET / PET-CT scan. However, there is no study to define the patterns of SPT on 18F-FDG PET / PET-CT scan, and to reveal metabolomics characteristics explaining high 18F-FDG uptake in SPT of the pancreas. Methods: mRNA expression for glucose metabolism was checked from 5 samples of SPT, pancreatic ductal adenocarcinoma (PCA), and paired normal pancreatic tissues. Differentially expressed genes between non-neoplastic pancreatic tissue and pancreatic tumors (SPN, or PCA) were determined as those with p<0.01 and a fold change >1.5. The expressions of selected genes for glucose metabolism in SPT were also confirmed by both western bolt and immunohistochemistry. Medical records of the patients with SPT who underwent pancreatectomy were retrospectively reviewed. Among them, 36 patients with preoperative 18F-FDG PET scan were selected. Clinical pattern of clinical pattern of SPT on 18F-FDG PET / PET-CT scan were classified according to the proportion of 18F-FDG uptake within the whole tumor volume (hot uptake: ≥70%, mixed: 30≤ <70, and defective: <30%). PET-based parameters, such as maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (TMV2.5), and total lesion glycolysis (TLG2.5) were evaluated. Correlation between pattern of 18F-FDG uptake, expression of glucose metabolism-related genes, and microscopic malignant features was performed.Results: Thirty-five patients (97.2%) were female and only one was male with age, 34.8±11.2 years. Clinical patterns of 18F-FDG uptake were categorized into three types; hot-uptake (N=19), mixed (N=5), and defective type (N=12). Radiologic tumor size, SUVmax, SUVmean , and TLG2.5 were significant different according to pattern of 18F-FDG uptake (ANOVA, p<0.05). It was observed that glucose metabolism-related genes, such as GLUT1, HK1, PFKM, ENO2, PKM2 were highly expressed in SPTs in both mRNA and protein level. Comparing with hot+mixed type, defective type of SPTs showed lower expression of HK1 (p=0.014), PKM2 (p=0.028), and Ki-67 (p=0.070) with frequent intratumoral necrosis (p=0.007). High Ki-67 expression (≥3%) was associated with high SUVmax of SPT of the pancreas (p=0.002). In addition, defective type of SPT tended to be associated with benign microscopic features (p=0.070). In literatures review, hot+ mixed type of SPTs appeared to be more aggressive comparing to defective type of SPTs.Conclusion: This study is the first investigation to dissect metabolomic characteristics of SPT of the pancreas. Basically, SPT cells harbor active molecular capacity for increasing glucose metabolism, and it was well visualized in 18F-FDG-PET/ PET-CT scan. Therefore, clinical patterns of 18F-FDG uptake in SPTs can be influenced according to intratumoral hemorrhagic necrosis and can be classified as three types; hot uptake, mixed, and defective type. Form the view point of metabolomics, defective type of SPTs was associated with low metabolic activity and apparently related to low Ki-67 index, suggesting there is some room for reserving surgery in this type of SPTs. Further study needs to be conducted to identify metabolomics differences between indolent and aggressive STPs of the pancreas.