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

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Title:	Prognostic value of WHO grade in pancreatic neuro-endocrine tumors in Multiple Endocrine Neoplasia type 1: Results from the DutchMEN1 Study Group
Author(s):	Conemans, E.B.; Brosens, L.A.A. ; Raicu-Ionita, G.M.; Pieterman, C.R.; Herder, W.W. de; Dekkers, O.M.; Hermus, A.R.M.M. ; Horst-Schrivers, A.N. van der; Bisschop, P.H.; Havekes, B.; Drent, M.L.; Timmers, H.T.M.; Offerhaus, G.J.; Valk, G.D.; Vriens, M.R.
Publication year:	2017
Source:	Pancreatology, vol. 17, iss. 5, (2017), pp. 766-772
ISSN:	1424-3903
DOI:	https://doi.org/10.1016/j.pan.2017.07.196
Publication type:	Article / Letter to editor
Please use this identifier to cite or link to this item : http://hdl.handle.net/2066/177419
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Subject:	Radboudumc 14: Tumours of the digestive tract RIMLS: Radboud Institute for Molecular Life Sciences Radboudumc 16: Vascular damage RIHS: Radboud Institute for Health Sciences
Organization:	Pathology Internal Medicine
Journal title:	Pancreatology
Volume:	vol. 17
Issue:	iss. 5
Page start:	p. 766
Page end:	p. 772
Abstract:	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.