Prognostic value of WHO grade in pancreatic neuro-endocrine tumors in Multiple Endocrine Neoplasia type 1: Results from the DutchMEN1 Study Group
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.
|Keywords||Liver metastases, Multiple endocrine neoplasia type 1, Pancreatic neuroendocrine tumors, Prognosis, WHO grade|
|Persistent URL||dx.doi.org/10.1016/j.pan.2017.07.196, hdl.handle.net/1765/101670|
Conemans, E.B, Brosens, L.A, Raicu-Ionita, G.M. (Gabriela M.), Pieterman, C.R.C, de Herder, W.W, Dekkers, O.M, … 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, 766–772. doi:10.1016/j.pan.2017.07.196