Prognostic value of WHO grade in pancreatic neuro-endocrine tumors in Multiple Endocrine Neoplasia type 1: 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

doi:10.1016/j.pan.2017.07.196

Prognostic value of WHO grade in pancreatic neuro-endocrine tumors in Multiple Endocrine Neoplasia type 1: 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

22 Citations (Web of Science)

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

Original language	English
Pages (from-to)	766-772
Number of pages	7
Journal	Pancreatology
Volume	17
Issue number	5
DOIs	https://doi.org/10.1016/j.pan.2017.07.196
Publication status	Published - 2017

Keywords

Multiple endocrine neoplasia type 1
Pancreatic neuroendocrine tumors
Liver metastases
WHO grade
Prognosis
KI67 PROLIFERATIVE INDEX
NATURAL-HISTORY
MEN1
CLASSIFICATION
EPIDEMIOLOGY
SURVIVAL
DEATH
GTE

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10.1016/j.pan.2017.07.196

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Conemans, E. B., Brosens, L. A. A., Raicu-Ionita, G. M., Pieterman, C. R. C., de Herder, W. W., Dekkers, O. M., Hermus, A. R., van der Horst-Schrivers, A. N., Bisschop, P. H., Havekes, B., Drent, M. L., Timmers, H. T. M., Offerhaus, G. J., Valk, G. D., & Vriens, M. R. (2017). Prognostic value of WHO grade in pancreatic neuro-endocrine tumors in Multiple Endocrine Neoplasia type 1: Results from the DutchMEN1 Study Group. Pancreatology, 17(5), 766-772. https://doi.org/10.1016/j.pan.2017.07.196

@article{4e95fd6941fd417a89b0971459a137e1,

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

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 tumorsConclusion: 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.",

keywords = "Multiple endocrine neoplasia type 1, Pancreatic neuroendocrine tumors, Liver metastases, WHO grade, Prognosis, KI67 PROLIFERATIVE INDEX, NATURAL-HISTORY, MEN1, CLASSIFICATION, EPIDEMIOLOGY, SURVIVAL, DEATH, GTE",

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

year = "2017",

doi = "10.1016/j.pan.2017.07.196",

language = "English",

volume = "17",

pages = "766--772",

journal = "Pancreatology",

issn = "1424-3903",

publisher = "Elsevier",

number = "5",

}

Conemans, EB, Brosens, LAA, Raicu-Ionita, GM, Pieterman, CRC, de Herder, WW, Dekkers, OM, Hermus, AR, van der Horst-Schrivers, AN, Bisschop, PH, Havekes, B, Drent, ML, Timmers, HTM, Offerhaus, GJ, Valk, GD & Vriens, MR 2017, 'Prognostic value of WHO grade in pancreatic neuro-endocrine tumors in Multiple Endocrine Neoplasia type 1: Results from the DutchMEN1 Study Group', Pancreatology, vol. 17, no. 5, pp. 766-772. https://doi.org/10.1016/j.pan.2017.07.196

TY - JOUR

T1 - Prognostic value of WHO grade in pancreatic neuro-endocrine tumors in Multiple Endocrine Neoplasia type 1

T2 - Results from the DutchMEN1 Study Group

AU - Conemans, Elfi B.

AU - Brosens, Lodewijk A. A.

AU - Raicu-Ionita, Gabriela M.

AU - Pieterman, Carolina R. C.

AU - de Herder, Wouter W.

AU - Dekkers, Olaf M.

AU - Hermus, Ad R.

AU - van der Horst-Schrivers, Anouk N.

AU - Bisschop, Peter H.

AU - Havekes, Bas

AU - Drent, Madeleine L.

AU - Timmers, H. Th Marc

AU - Offerhaus, G. Johan

AU - Valk, Gerlof D.

AU - Vriens, Menno R.

PY - 2017

Y1 - 2017

N2 - 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 tumorsConclusion: 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.

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 tumorsConclusion: 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.

KW - Multiple endocrine neoplasia type 1

KW - Pancreatic neuroendocrine tumors

KW - Liver metastases

KW - WHO grade

KW - Prognosis

KW - KI67 PROLIFERATIVE INDEX

KW - NATURAL-HISTORY

KW - MEN1

KW - CLASSIFICATION

KW - EPIDEMIOLOGY

KW - SURVIVAL

KW - DEATH

KW - GTE

U2 - 10.1016/j.pan.2017.07.196

DO - 10.1016/j.pan.2017.07.196

M3 - Article

C2 - 28811081

SN - 1424-3903

VL - 17

SP - 766

EP - 772

JO - Pancreatology

JF - Pancreatology

IS - 5

ER -