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High-grade progression confers poor survival in pancreatic neuroendocrine tumors.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
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2019 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194Article in journal (Refereed) Epub ahead of print
Abstract [en]

INTRODUCTION: Little is known about how Pancreatic Neuroendocrine Tumors (PanNETs) evolve over time and if changes towards a more aggressive biology correlates with prognosis. The purpose of this study was to characterize changes PanNET differentiation and proliferation over time, and to correlate findings to overall survival (OS).

PATIENTS AND METHODS: In this retrospective cohort study we screened 475 PanNET patients treated at Uppsala University Hospital, Sweden. Sporadic patients with baseline and follow-up tumor samples were included. Pathology reports and available tissue sections were re-evaluated with regard to tumor histopathology and Ki-67 index.

RESULTS: Forty-six patients with 106 tumor samples (56 available for pathology re-evaluation) were included. Median Ki-67 index at diagnosis was 7% (range 1-38%), grade 1 n=8, grade 2 n=36, and grade 3 n=2. The median change in Ki-67 index (absolute value; follow-up - baseline) was +14% (range -11 to +80%). Increase in tumor grade occurred in 28 patients (63.6%), the majority from grade 1/2 to grade 3 (n=24, 54.5%). The patients with a high-grade progression had a median OS of 50.2 months compared to 115.1 months in patients without such progression (HR 3.89, 95% CI 1.91-7.94, P<0.001).

CONCLUSIONS: A longitudinal increase in Ki-67 index and increase in tumor grade were observed in a majority of PanNETs included in this study. We propose that increase in Ki-67 index and high-grade progression should be investigated further as important biomarkers in PanNET.

Place, publisher, year, edition, pages
2019.
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Cancer and Oncology Clinical Laboratory Medicine
Research subject
Oncology; Pathology
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URN: urn:nbn:se:uu:diva-399943DOI: 10.1159/000504392PubMedID: 31658459OAI: oai:DiVA.org:uu-399943DiVA, id: diva2:1379509
Available from: 2019-12-17 Created: 2019-12-17 Last updated: 2020-02-05Bibliographically approved

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Botling, JohanBajic, DraganNorlén, OlovLönngren, VincentEriksson, BarbroWelin, StaffanHellman, PerSkogseid, BrittCrona, Joakim

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Botling, JohanBajic, DraganNorlén, OlovLönngren, VincentEriksson, BarbroWelin, StaffanHellman, PerSkogseid, BrittCrona, Joakim
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Science for Life Laboratory, SciLifeLabClinical and experimental pathologyDepartment of Medical SciencesDepartment of Surgical Sciences
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Neuroendocrinology
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