High rate of Ki-67 increase in entero-pancreatic NET relapses after surgery with curative intent.

Elettra Merola*, Aurel Perren, Anja Rinke, A Zerbi, MG McNamara, R Arsenic, Nicola Fazio, W.W. de Herder, JW Valle, T. M. Gress, B Wiedenmann, Andreas Pascher, Marianne E. Pavel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)


Neuroendocrine neoplasms (NENs) present with advanced disease at diagnosis in up to 28% of cases, precluding the possibility of curative-intent surgery. Histopathological heterogeneity of this disease can be observed inter-individually as well as intra-individually during disease course. The present study aimed to assess the frequency of Ki-67 change after radical surgery, in a series of patients with radically resected entero-pancreatic neuroendocrine tumors (EP-NETs).

We present the analysis of a multicenter, retrospective, series of EP-NETs G1–G2 recurring after radical resection and with histological re-evaluation at disease recurrence (DR). The primary endpoint was the description of Ki-67 change at DR compared to time of surgery. The secondary endpoint was assessment of recurrence-free survival (RFS) rates. In total, 47 patients had a second histological evaluation and could be included in the present study. Median Ki-67 at surgery was 3% (range 1–15%) but, at DR, a significant increase in the value was observed (7%, range 1–30%; p < .01) and involved 66.0% of cases, with a corresponding increase in tumor grading in 34.0% (p = .05). Median RFS of the overall population was 40 months, and was worse when Ki-67 increased at DR vs. stable Ki-67 value (36 vs. 61 months, respectively; p = .02). In conclusion, in more than half of the cases with relapse after radical surgery, a higher proliferative index with a potentially more aggressive potential was observed. Therefore, histological reassessment should be considered on DR because tailored therapeutic strategies may be required for these patients.
Original languageEnglish
Article numbere13193
JournalJournal of Neuroendocrinology
Issue number10
Publication statusPublished - Oct 2022

Bibliographical note

Funding Information:
The study was supported by the European Neuroendocrine Tumor Society (ENETS) “Excellence Academy Fellowship Grant” (2017).

Funding Information:
Dr Mairéad G. McNamara has received research grant support from Servier, Ipsen and NuCana. She has received travel and accommodation support from Bayer and Ipsen and speaker honoraria from Pfizer, Ipsen, NuCana, Mylan and Advanced Accelerator Applications (UK & Ireland) Ltd. She has served on advisory boards for Celgene, Ipsen, Sirtex, Baxalta and Incyte. Dr Valle reports personal fees from Agios, AstraZeneca, Baxter, Genoscience Pharma, Hutchison Medipharma, Imaging Equipment Ltd (AAA), Incyte, Ipsen, Mundipharma EDO, Mylan, QED, Servier, Sirtex and Zymeworks, as well as and grants, personal fees and non‐financial support from NuCana, all outside the submitted work. Anja Rinke has received honoraria for presentations or advisory board attendance from AAA, Advanz Pharma, Falk, Ipsen Pharma and Novartis Pharma without any relation to the submitted work. The other authors declare that have no conflicts of interest.

Publisher Copyright:
© 2022 British Society for Neuroendocrinology.


Dive into the research topics of 'High rate of Ki-67 increase in entero-pancreatic NET relapses after surgery with curative intent.'. Together they form a unique fingerprint.

Cite this