Aberrant expression of the simple mucin‐type carbohydrate antigens such as T, Tn, sialyl‐T and sialyl‐Tn is associated with poor prognosis in several cancers. β1,3‐N‐acetylglucosaminyltransferase‐3 (B3GNT3), a member of the β3GlcNAcT family, is responsible for forming extended core 1 (T antigen) oligosaccharides. The role of B3GNT3, which is expressed in various tissues including human fetal brain, in regulating neuroblastoma (NB) formation and cell behaviors remains unclear. Here, we showed that increased B3GNT3 expression evaluated using immunohistochemistry in NB tumor tissues correlated well with the histological grade of differentiation as well as a favorable Shimada's subset of pathology. Univariate and multivariate analyses revealed that positive B3GNT3 expression in tumor tissues predicted a favorable prognosis in NB patients independent of other prognostic markers. B3GNT3 overexpression suppresses T antigen formation and malignant phenotypes including migration and invasion of SK‐N‐SH cells, whereas B3GNT3 knockdown enhances these phenotypes of SK‐N‐SH cells. Moreover, B3GNT3 expression decreased phosphorylation of focal adhesion kinase (FAK), Src, paxillin, Akt and ERK1/2. We conclude that B3GNT3 predicts a favorable cancer behavior of NB and suppresses malignant phenotypes by modulating mucin‐type O‐glycosylation and signaling in NB cells.

Neuroblastic tumors are childhood neoplasms that possess amino acid decarboxylase (AADC) activity and can theoretically be imaged by ¹⁸F-fluorodihydroxyphenylalanine (¹⁸F-FDOPA) PET, a new diagnostic tool for neuroendocrine tumors. In this study, we explored the accuracy and clinical role of ¹⁸F-FDOPA PET in neuroblastic tumors. Methods: From 2008 to 2011, patients with tissue-proven neuroblastic tumors receiving ¹⁸F-FDOPA PET at initial diagnosis or during follow-ups were enrolled. The sensitivity and specificity of ¹⁸F-FDOPA PET were compared with those of ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) scintigraphy and ¹⁸F-FDG PET, using tumor histology as the standard. The maximum standardized uptake value and tumor-to-liver uptake ratio on ¹⁸F-FDOPA PET were measured and correlated with AADC messenger RNA level in tumor tissue. Results: Fifty tumors from 34 patients, including 42 neuroblastic tumors and 8 lesions without viable tumor cells, were eligible for analysis. ¹⁸F-FDOPA PET successfully detected neuroblastic tumors of different histologic types in various anatomic sites, at a sensitivity of 97.6% (87.4%–99.9%) and a specificity of 87.5% (47.3%–99.7%). In tumors with concomitant studies, ¹⁸F-FDOPA PET demonstrated a higher sensitivity than ¹²³I-MIBG scintigraphy (n = 18; P = 0.0455) or ¹⁸F-FDG PET (n = 46; P = 0.0455). Among the 18 tumors with concomitant ¹²³I-MIBG scans, 4 tumors with viable cells were ¹²³I-MIBG–negative but were successfully detected by ¹⁸F-FDOPA PET. The tumor uptake of ¹⁸F-FDOPA significantly correlated with AADC expression (n = 15 nonhepatic tumors; maximum standardized uptake value, P = 0.0002; tumor-to-liver uptake ratio, P < 0.0001). Conclusion: ¹⁸F-FDOPA PET showed high sensitivity and specificity in detecting and tracking neuroblastic tumors in this preliminary study with a small cohort of patients and might be complementary to ¹²³I-MIBG scintigraphy and ¹⁸F-FDG PET. By correlating with AADC expression, ¹⁸F-FDOPA PET might serve as a useful imaging tool for the functional assessment of neuroblastic tumors.

This study determined the prognostic value of volumetric parameters derived from pretreatment F-FDG and F-DOPA PET/CT of neuroblastoma and their correlation with clinical and histopathologic features. A total of 25 children with neuroblastoma underwent pretreatment F-FDG and F-DOPA PET/CT within 4 weeks. The SUVmax of primary tumors on F-FDG and F-DOPA PET were recorded as SUVFDG and SUVDOPA, respectively. For volumetric parameters of primary tumors, 40% of SUVmax was used to generate volume of interest. If the 40% of SUVmax was below 2.5, an SUV threshold of 2.5 was used instead. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), dopaminergic tumor volume (DTV), and total lesion F-DOPA activity (TLDA) were recorded as F-FDG and F-DOPA volumetric parameters. All indices were compared between groups distinguished by survival status and clinical features, including bone marrow involvement, lymph node metastasis, amplification of the MYCN oncogene, invasive features on anatomic images, and risk categories. The Kaplan-Meier method and log-rank test were used to compare the survival curves between groups. The median follow-up period was 28.2 months. Nonsurvivors (20%) tended to have lower SUVDOPA, DTV, and TLDA (P ≤ 0.05), and higher SUVFDG, MTV, and TLG (all P < 0.05). Lower F-DOPA uptake is associated with bone marrow and lymph node metastases (all P < 0.05). Higher F-FDG uptake is associated with MYCN amplification (all P < 0.05) and anatomic invasive features of tumors such as vascular encasement or adjacent organ invasion (TLG, P = 0.05). Only volumetric indices (DTV, TLDA, MTV, and TLG) significantly differed among risk groups (all P < 0.05). Pretherapeutic F-DOPA and F-FDG PET provided complementary information, and both can be served for risk stratification. Volumetric indices of F-DOPA and F-FDG PET correlate more highly with risk grouping.