Prognostic value of WHO grade in pancreatic neuro-endocrine tumors in Multiple Endocrine Neoplasia type 1: Results from the DutchMEN1 Study Group: Results from the DutchMEN1 Study Group

Elfi B. Conemans, Lodewijk A. A. Brosens, Gabriela M. Raicu-Ionita, Carolina R. C. Pieterman, Wouter W. de Herder, Olaf M. Dekkers, Ad R. Hermus, Anouk N. van der Horst-Schrivers, Peter H. Bisschop, Bas Havekes, Madeleine L. Drent, H. Th Marc Timmers, G. Johan Offerhaus, Gerlof D. Valk, Menno R. Vriens

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Background: The prognostic value of WHO grade in pancreatic neuroendocrine tumors (PanNETs) in patients with Multiple Endocrine Neoplasia Type 1 (MEN1) is unknown. Methods: We performed a cohort study using the Dutch National MEN1 database, which includes >90% of the Dutch MEN1 population with data collected between 1990 and 2014. Formalin-fixed paraffin embedded tissue blocks from the largest resected PanNET per patient were collected. MIB1 staining was performed and KI67 labeling index (LI) was determined by manual eye-counting under a microscope and by digital image analysis. Mitotic count was evaluated from hematoxylin & eosin stains. Association between WHO grade and (time until) development of liver metastases was calculated. Results: Sixty-nine MEN1 patients who underwent pancreatic surgery were included. Ten patients (14%) developed liver metastases and all had PanNETs >= 3 cm. WHO G1, G2 and G3 PanNETs were seen in 83% (n = 57), 16% (n = 11) and 1% (n = 1) respectively. In non-functioning PanNETs >2 cm, liver metastases occurred in 80% of WHO G2 PanNETs (4/5) compared to 23% (5/22) in WHO G1 PanNETs (p = 0.03) when WHO grade was based on mitotic count only. This significant association was not seen for WHO grade based on Ki67 LI. After five years, liver metastases in non-functioning PanNETs were not seen in tumors <= 2 cm, in 10% of the large WHO G1 (according to mitotic count only) tumors and in 60% of large WHO G2 tumors (p-value 0.000). Conclusion: High mitotic count is correlated with poor prognosis in MEN1 patients with large non-functioning PanNETs. (C) 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved
Original languageEnglish
Pages (from-to)766-772
Number of pages7
Issue number5
Early online date2017
Publication statusPublished - 1 Sept 2017


  • Liver metastases
  • Multiple endocrine neoplasia type 1
  • Pancreatic neuroendocrine tumors
  • Prognosis
  • WHO grade

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