Systematic comparison of sporadic and syndromic pancreatic islet cell tumors.

نویسندگان

  • Zoran Erlic
  • Ursula Ploeckinger
  • Alberto Cascon
  • Michael M Hoffmann
  • Laura von Duecker
  • Aurelia Winter
  • Gerit Kammel
  • Janina Bacher
  • Maren Sullivan
  • Berend Isermann
  • Lars Fischer
  • Andreas Raffel
  • Wolfram Trudo Knoefel
  • Matthias Schott
  • Tobias Baumann
  • Oliver Schaefer
  • Tobias Keck
  • Richard P Baum
  • Ioana Milos
  • Mihaela Muresan
  • Mariola Peczkowska
  • Andrzej Januszewicz
  • Kenko Cupisti
  • Anke Tönjes
  • Mathias Fasshauer
  • Jan Langrehr
  • Peter von Wussow
  • Abbas Agaimy
  • Günter Schlimok
  • Regina Lamberts
  • Thorsten Wiech
  • Kurt Werner Schmid
  • Alexander Weber
  • Mercedes Nunez
  • Mercedes Robledo
  • Charis Eng
  • Hartmut P H Neumann
چکیده

Pancreatic islet cell tumors (ICTs) occur as sporadic neoplasias or as a manifestation of multiple endocrine neoplasia type 1 (MEN1) and von Hippel-Lindau disease (VHL). Molecular classification of ICTs is mandatory for timely diagnosis and surveillance. Systematic comparison of VHL-ICTs and sporadic ICTs has been lacking. Our registry-based approaches used the German NET-Registry with 259 patients with neuroendocrine tumors (NETs), who were primarily diagnosed with NETs, and the German VHL-Registry with 485 molecular genetically confirmed patients who had undergone magnetic resonance imaging or computed tomography of the abdomen. All patients provided blood DNA for testing of the MEN1 and VHL genes for intragenic mutations and large deletions. In the NET-Registry, 9/101 patients (8.9%) with ICTs had germline mutations, 8 in MEN1 and 1 in VHL. In the VHL-Registry, prevalence of NETs was 52/487 (10.6%), and all were ICTs. Interestingly, of those with VHL p.R167W, 47% developed ICTs, compared to 2% of those with p.Y98H. In total, there were 92 truly sporadic, i.e. mutation-negative ICT patients. Comparing these with the 53 VHL-ICT patients, the statistically significant differences were predominance of female gender (P=0.01), multifocal ICTs (P=0.0029), and lower malignancy rate (P<0.001) in VHL-ICTs compared to sporadic cases. VHL was prevalent in <0.5% of NETs, while NETs occur in ∼10% of VHL, virtually exclusively as ICTs, which are rarely the first presentation. Patients with NETs should not be subjected to genetic testing of the VHL gene, unless they have multifocal ICTs, other VHL-associated tumors, and/or a family history for VHL.

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عنوان ژورنال:
  • Endocrine-related cancer

دوره 17 4  شماره 

صفحات  -

تاریخ انتشار 2010