臨床病理学ジャーナル

抽象的な

An Analysis of Prognostic Factors in Pancreatic Neuroendocrine Tumors

Moyana TN, Kendal WS, Shabana W, Walker A, Balaa FK, Nyiraneza C, Dawkins Y, Chatterjee A, Goodwin R, Asmis T and Chang N

Background: Pancreatic neuroendocrine tumors (PNETs) generally behave indolently. However, some manifest an aggressive clinical course with poor prognosis. It is not clear whether this is due to intrinsic tumor aggressiveness, dedifferentiation, or simply silent progressive tumor accumulation that then triggers complications. This study analysed the features of PNETs to gain further insight into their biology.
Methods: A retrospective clinicopathologic review of 74 PNETs using Kaplan-Meier and Cox proportional hazard analyses.
Results: Median overall survival was 117 months; 5 year survivals were 92% where the PNETs were resected versus 35% for those not resected (p<0.001). Liver metastases developed in 33/74 (18/33 synchronous metastases; 15/33 metachronous). There was a significant difference in Ki67 grade between metastatic and non-metastatic tumors (p<0.001). However, there was considerable overlap of grades between synchronous and metachronous tumor groups with 5/10 (50%) of synchronous PNETs being well-differentiated. Most patients with metachronous metastases (10/15; 67%) showed non-progressive disease whereas the majority with synchronous metastases (15/18; 83%) manifested progressive disease (p=0.01). On Cox analysis, synchronous metastases and inoperability were significant predictors of survival whereas Ki67 grade and T/N stage were not.
Conclusion: Aggressive PNETs were associated with synchronous metastases and inoperability. By multivariate analysis, the strongest adverse prognostic factor was synchronous metastases and this was related to the poor outcome over and above what was indicated by the Ki67 grade on univariate analysis. While it is not entirely clear whether the presence of synchronous metastases reflects intrinsic tumor aggressiveness or simply disease in the later stages of its natural history, our findings suggest that they reflect intrinsic aggressiveness de novo. However larger studies with more statistical power are required to further substantiate this. While cell proliferation markers such as Ki67 have greatly improved our grading and understanding of PNETs, molecular studies of events involved in the metastatic cascade could also be meritorious in elucidating disease biology.