Novel recurrence risk stratification of resected pancreatic neuroendocrine tumor

Gao, Heli; Liu, Liang; Wang, Wenquan; Xu, Huaxiang; Jin, Kaizhou; Wu, Chifei; Zhou, Qi; Zhang, Shirong; Liu, Chen; Xu, Jinzhi; Ni, Quanxing; Lei, Yu

doi:10.1016/j.canlet.2017.10.036

Cited by 44 publications

(33 citation statements)

References 23 publications

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“…Others have shown that the prognoses of patients with NF-PanNETs were poorer when compared to patients with functional PanNETs, especially for insulinoma, and were significantly better than patients with poorly differentiated PanNECs. [40][41][42] We found that the percentage of TLS in G1/G2 NF-PanNETs was lower than in G1/G2 functional PanNETs, although this difference was not statistically significant. Additionally, as the tumor grade increases, the percentage of TLS decreases significantly.…”

Section: Open Accessmentioning

confidence: 63%

“…Our institution also generated a recurrent-risk stage system based on independent predictors of recurrence in PanNETs including T stage, N stage, insulinoma and Ki67 index. 41 In contrast to these models, our newly constructed nomogram includes not only clinical characteristics but also immune microenvironment components-TLS, which might help us predict the prognosis of NF-PanNETs more accurately. Overall, our data indicate that our nomogram is as good, if not better than the aforementioned prognostic models of Genc, Ellison, and our own institution.…”

Section: Open Accessmentioning

confidence: 99%

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Infiltrating pattern and prognostic value of tertiary lymphoid structures in resected non-functional pancreatic neuroendocrine tumors

Zhang

Wang

Han

et al. 2020

J Immunother Cancer

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BackgroundTertiary lymphoid structures (TLS) are associated with favorable survival and play a critical role in most solid tumors. However, investigations of TLS are lacking in patients with grade 1 or grade 2 (G1/G2) non-functional pancreatic neuroendocrine tumors (NF-PanNETs). This study aimed to investigate the presence, cellular composition, association with tumor-infiltrating immune cells, and prognostic value of TLS in G1/G2 NF-PanNETs.MethodsTumor tissues from a 182-patient Fudan cohort and a 125-patient external validation set were assessed by H&E staining, immunohistochemistry, and/or multispectral fluorescent immunohistochemistry.ResultsTLS were identified in more than one-third of patients with G1/G2 NF-PanNETs and were located peritumorally, either just outside the tumor tissue or in the stromal area. TLS were mainly composed of B-cell follicles with germinal centers and T-cell zones with dendritic cells. Kaplan-Meier analyses showed that the presence of TLS correlated with both longer recurrence-free survival (RFS, p<0.001) and overall survival (OS, p=0.001), but the number of TLS had no prognostic significance. Multivariate Cox-regression analyses demonstrated that the presence of TLS, WHO classification, and 8th edition American Joint Committee on Cancer (AJCC8th) tumor-node-metastasis (TNM) stage were independent prognostic factors for RFS (p=0.004, p=0.001, and p<0.001, respectively) and OS (p=0.009, p=0.008, and p=0.019, respectively). These results were confirmed using an external validation set. Finally, a nomogram incorporating the presence of TLS was constructed to predict the probability of 5-year RFS of resected G1/G2 NF-PanNETs, which improved on the current WHO classification and AJCC8th TNM stage.ConclusionsThe presence of TLS is an independent and favorable predictor of resected G1/G2 NF-PanNETs, which may play a role in cancer immunobiology.

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Section: Open Accessmentioning

confidence: 63%

Section: Open Accessmentioning

confidence: 99%

Infiltrating pattern and prognostic value of tertiary lymphoid structures in resected non-functional pancreatic neuroendocrine tumors

Zhang

Wang

Han

et al. 2020

J Immunother Cancer

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“…Studies have established a risk stratification to predict recurrence by combining TNM stage, Ki-67, 10 and functionality. 5 However, the identification of patients with high risk for recurrence remains challenging.…”

Section: Introductionmentioning

confidence: 99%

CLEC3A, MMP7, and LCN2 as novel markers for predicting recurrence in resected G1 and G2 pancreatic neuroendocrine tumors

et al. 2019

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Although the postoperative recurrence rate for pancreatic neuroendocrine tumors (PNETs) is reported to be 13.5%‐30%, the paucity of valuable biomarkers to predict recurrence poses a problem for the early detection of relapse. Hence, this study aimed to identify new biomarkers to predict the recurrence of PNETs. We performed RNA sequencing (RNA‐Seq) on RNA isolated from frozen primary tumors sampled from all localized G1/G2 PNETs resected curatively from 1998 to 2015 in our institution. We calculated differentially expressed genes (DEGs) in tumor with and without recurrence (≥3 years) for the propensity‐matched cohort. Gene ontology analysis for the identified DEGs was also performed. Furthermore, we evaluated the expression levels of candidate genes as recurrence predictors via immunostaining. Comparison of transcriptional levels in tumors with and without recurrence identified 166 DEGs. Up‐ and downregulated genes with high significance in these tumors were mainly related to extracellular organization and cell adhesion, respectively. We observed the top three upregulated genes, C‐type lectin domain family 3 member A (CLEC3A), matrix metalloproteinase‐7 (MMP7), and lipocalin2 (LCN2) immunohistochemically and compared their levels in recurrent and nonrecurrent tumors. Significantly higher recurrence rate was shown in patients with positive expression of CLEC3A ( P = 0.028), MMP7 ( P = 0.003), and LCN2 ( P = 0.040) than that with negative expression. We identified CLEC3A, MMP7, and LCN2 known to be associated with the phosphatidylinositol‐3‐kinase/Akt pathway, as potential novel markers to predict the postoperative recurrence of PNETs.

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“…Despite a 5-year survival rate for resected patient is around 90%, recurrence rate is 12-25% at five years and late recurrence were described (up to 70% at 15 years) [117][118][119][120][121]. Follow-up requires a close monitoring with physical examination, biology (essentially for F-pNETS) and cross-sectional imaging (CT/MRI), 3-6 monthly for NF-pNETs and 6-12 monthly for F-pNETs every year for three years, every 1-2 years thereafter, and until 10 years post-pancreatectomy.…”

Section: Recurrence Rate and Follow-up After Resectionmentioning

confidence: 97%

Surgical Management of Neuroendocrine Tumours of the Pancreas

Souche

Hobeika

Hain

et al. 2020

JCM

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Neuroendocrine tumours of the pancreas (pNET) are rare, accounting for 1–2% of all pancreatic neoplasms. They develop from pancreatic islet cells and cover a wide range of heterogeneous neoplasms. While most pNETs are sporadic, some are associated with genetic syndromes. Furthermore, some pNETs are ‘functioning’ when there is clinical hypersecretion of metabolically active peptides, whereas others are ‘non-functioning’. pNET can be diagnosed at a localised stage or a more advanced stage, including regional or distant metastasis (in 50% of cases) mainly located in the liver. While surgical resection is the cornerstone of the curative treatment of those patients, pNET management requires a multidisciplinary discussion between the oncologist, radiologist, pathologist, and surgeon. However, the scarcity of pNET patients constrains centralised management in high-volume centres to provide the best patient-tailored approach. Nonetheless, no treatment should be initiated without precise diagnosis and staging. In this review, the steps from the essential comprehensive preoperative evaluation of the best surgical approach (open versus laparoscopic, standard versus sparing parenchymal pancreatectomy, lymphadenectomy) according to pNET staging are analysed. Strategies to enhance the short- and long-term benefit/risk ratio in these particular patients are discussed.

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Novel recurrence risk stratification of resected pancreatic neuroendocrine tumor

Cited by 44 publications

References 23 publications

Infiltrating pattern and prognostic value of tertiary lymphoid structures in resected non-functional pancreatic neuroendocrine tumors

Infiltrating pattern and prognostic value of tertiary lymphoid structures in resected non-functional pancreatic neuroendocrine tumors

CLEC3A, MMP7, and LCN2 as novel markers for predicting recurrence in resected G1 and G2 pancreatic neuroendocrine tumors

Surgical Management of Neuroendocrine Tumours of the Pancreas

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