PMID- 28811081
OWN - NLM
STAT- MEDLINE
DCOM- 20180611
LR  - 20180611
IS  - 1424-3911 (Electronic)
IS  - 1424-3903 (Linking)
VI  - 17
IP  - 5
DP  - 2017 Sep-Oct
TI  - Prognostic value of WHO grade in pancreatic neuro-endocrine tumors in Multiple 
      Endocrine Neoplasia type 1: Results from the DutchMEN1 Study Group.
PG  - 766-772
LID - S1424-3903(17)30718-4 [pii]
LID - 10.1016/j.pan.2017.07.196 [doi]
AB  - 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.
CI  - Copyright (c) 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.
FAU - Conemans, Elfi B
AU  - Conemans EB
AD  - Department of Endocrine Surgical Oncology, University Medical Center Utrecht, 
      Utrecht, The Netherlands; Department of Endocrine Oncology, University Medical 
      Center Utrecht, Utrecht, The Netherlands.
FAU - Brosens, Lodewijk A A
AU  - Brosens LAA
AD  - Department of Pathology, University Medical Center Utrecht, Utrecht, The 
      Netherlands.
FAU - Raicu-Ionita, Gabriela M
AU  - Raicu-Ionita GM
AD  - Department of Pathology, University Medical Center Utrecht, Utrecht, The 
      Netherlands.
FAU - Pieterman, Carolina R C
AU  - Pieterman CRC
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The 
      Netherlands.
FAU - de Herder, Wouter W
AU  - de Herder WW
AD  - Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The 
      Netherlands.
FAU - Dekkers, Olaf M
AU  - Dekkers OM
AD  - Departments of Endocrinology and Metabolism and Clinical Epidemiology, Leiden 
      University Medical Center, Leiden, The Netherlands.
FAU - Hermus, Ad R
AU  - Hermus AR
AD  - Department of Endocrinology, Radboud University Medical Center, Nijmegen, The 
      Netherlands.
FAU - van der Horst-Schrivers, Anouk N
AU  - van der Horst-Schrivers AN
AD  - Department of Endocrinology, University of Groningen, University Medical Center 
      Groningen, Groningen, The Netherlands.
FAU - Bisschop, Peter H
AU  - Bisschop PH
AD  - Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, 
      The Netherlands.
FAU - Havekes, Bas
AU  - Havekes B
AD  - Department of Internal Medicine, Division of Endocrinology, Maastricht University 
      Medical Center, Maastricht, The Netherlands.
FAU - Drent, Madeleine L
AU  - Drent ML
AD  - Department of Internal Medicine, Section of Endocrinology, VU University Medical 
      Center, Amsterdam, The Netherlands.
FAU - Timmers, H Th Marc
AU  - Timmers HTM
AD  - Molecular Cancer Research, Regenerative Medicine Center, Center for Molecular 
      Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
FAU - Offerhaus, G Johan
AU  - Offerhaus GJ
AD  - Department of Pathology, University Medical Center Utrecht, Utrecht, The 
      Netherlands.
FAU - Valk, Gerlof D
AU  - Valk GD
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The 
      Netherlands.
FAU - Vriens, Menno R
AU  - Vriens MR
AD  - Department of Endocrine Surgical Oncology, University Medical Center Utrecht, 
      Utrecht, The Netherlands. Electronic address: mvriens@umcutrecht.nl.
LA  - eng
PT  - Journal Article
DEP - 20170731
PL  - Switzerland
TA  - Pancreatology
JT  - Pancreatology : official journal of the International Association of 
      Pancreatology (IAP) ... [et al.]
JID - 100966936
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*classification/epidemiology/surgery
MH  - Netherlands/epidemiology
MH  - Pancreatic Neoplasms/*classification/epidemiology/surgery
MH  - Prognosis
MH  - *World Health Organization
OTO - NOTNLM
OT  - Liver metastases
OT  - Multiple endocrine neoplasia type 1
OT  - Pancreatic neuroendocrine tumors
OT  - Prognosis
OT  - WHO grade
EDAT- 2017/08/16 06:00
MHDA- 2018/06/12 06:00
CRDT- 2017/08/17 06:00
PHST- 2017/01/06 00:00 [received]
PHST- 2017/07/28 00:00 [revised]
PHST- 2017/07/30 00:00 [accepted]
PHST- 2017/08/16 06:00 [pubmed]
PHST- 2018/06/12 06:00 [medline]
PHST- 2017/08/17 06:00 [entrez]
AID - S1424-3903(17)30718-4 [pii]
AID - 10.1016/j.pan.2017.07.196 [doi]
PST - ppublish
SO  - Pancreatology. 2017 Sep-Oct;17(5):766-772. doi: 10.1016/j.pan.2017.07.196. Epub 
      2017 Jul 31.