ECE2017 Guided Posters Endocrine Tumours (13 abstracts)
VHL Genotype and risk stratification of pancreatic neuroendocrine tumors in patients with von hippel-lindau disease
Amit Tirosh 1, , Jasmine Shell 3 , Patience Green 3 , Xavier M. Keutgen 4 , Samira M. Sadowski 5 , Mustapha el Lakis 3 , Pavel Nockel 3 , Dhaval Patel 3 , Naris Nilubol 3 & Electron Kebebew 3
1National Institutes of Health, Bethesda, MD, USA; 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Endocrine Oncology Branch, National Cancer Institute, Bethesda, MD, USA; 4Department of Surgery, Rush University Medical Center, Chicago, IL, USA; 5Endocrine and Thoracic Surgery, University Hospitals of Geneva, Geneva, Switzerland.
Background: About 8–20% of patients with von Hippel-Lindau disease (vHLd) develop pancreatic neuroendocrine tumors (PNETs). However, prognostic markers for these tumors are lacking. The VHL gene mutation type is associated with the clinical phenotype of vHLd. Hence, we aimed to determine whether VHL mutation characteristics may be associated with PNETs phenotype in patients with vHLd.
Methods: A prospective study of patients with vHLd and PNETs with follow-up imaging. VHL mutation type and position were defined using Sanger sequencing of germline DNA.
Results: 182 patients (476 PNETs) were followed for a median of 52 months (range 3–84). The VHL gene was sequenced in 154 patients: 75 patients (48.7%) had a missense mutation [MisM], 51 (33.1%) - deletion, 12 (7.8%) - nonsense, one (0.6%) - rearrangement, and 15 (9.7%) had frameshift mutations. Patients with a largest lesion diameter <1.2 cm had a lower risk for metastases (Log-Rank test, P=0.006) compared with larger diameters, whereas those with diameter >3 cm had higher risk for metastases compared with other patients (Log Rank test, P=0.007). Patients with MisM had a higher risk of requiring an intervention (Log-Rank test P=0.01) and for developing metastases during follow-up (P=0.007) compared to those with other mutation types. Among patients with a largest lesion diameter between 1.2 and 3 cm, those with MisM had higher risk for metastases (Log-Rank test, P=0.048) compared to other mutation types, and patients with mutation positioned in exon 3 of the VHL gene had higher risk for requiring intervention both in univariate (P=0.03) and multivariate analysis (Hazard ratio 2.9, 95% confidence interval 1.2–7.2, P=0.02).
Conclusion: Lesion diameter should be the pivot factor in directing PNETs management in vHLd. Among patients with a largest PNET diameter >1.2 and <3 cm, VHL genotyping may be useful for risk stratification.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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