Expression of p27Kip1 and p18Ink4c in human multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors

Abstract

These findings indicate that loss of p18, but not p27, is a common event in the development of MEN1-related PanNETs. Restoration of p18 function through CDK4/6 inhibitors could be a therapeutic option for MEN1-related PanNETs.

Enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumors

“…Next we examined tissue microarrays representing 77 Dutch PNETs 35 , 61 of which (79%) had germline MEN1 mutations, including 13 insulinomas associated with hyperinsulinemia (Supplementary Table 5). Overall, 34 of the 77 cases showed nuclear expression of ARX only (31% type A), 31 expressed only PDX1 (37% type B), and 12 cases were either double-positive (DP) or double-negative (DN – 8% each, Fig.…”

DNA methylation profiling in MEN1-related pancreatic neuroendocrine tumors reveals a potential epigenetic target for treatment

“…Both MEN1-related and sporadic well-differentiated PanNETs were included in this study. Selection of PanNET tissue from MEN1 patients has been described extensively before (15). In summary, the longitudinal DutchMEN1 Study Group (DMSG) database, which covers >90% of the Dutch MEN1 population aged 16 years and older, was used.…”

“…Immunohistochemistry for menin in sporadic PanNETs was performed on tissue micro-array slides including a subset of the sporadic cohort using a polyclonal antibody for menin (Bethyl Laboratories, A300-105A, 1:1600, ARS pH 5.8 pre-treatment and incubation at room temperature for 1 h). Menin staining was considered either positive (>30% positive nuclei) or negative (≤30% positive nuclei) (15).…”

‘Quality in, quality out’, a stepwise approach to evidence-based medicine for rare diseases promoted by multiple endocrine neoplasia type 1

“…Up till now, publications from the retrospective database have already answered many of our research questions and clinical management has changed Table 5 ( 4 , 6 , 7 , 14 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ). Moreover, the retrospective study design proved to be suitable, since a long latency between exposure and outcome exists.…”

“…Additional events appear necessary for pNETs to progress. Future studies should be aimed at identifying these molecular driving events, which could be used as potential biomarkers Expression of p27Kip1 and p18Ink4c in human multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors ( 39 ) To assess the role of role p27Kip1 and p18Ink4c in MEN1-related pancreatic neuroendocrine tumor development These findings indicate that loss of p18Ink4c, but not p27Kip1, is a common event in the development of MEN1-related pNETs. Restoration of p18Ink4c function through CDK4/6 inhibitors could be a therapeutic option for MEN1-related pNETs High fear of disease occurrence is associated with low quality of life in patients with multiple endocrine neoplasia type 1: results from the Dutch MEN1 Study Group ( 41 ) To assess whether MEN1 leads to psychological distress because of fear of disease occurrence (FDO), and affects quality of life The majority of patients with MEN1 have FDO for themselves and even more for their relatives.…”