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Poster Discussion – NETs and endocrine tumours

1590 - Longitudinal Increase in Ki67 and High-grade Transformation in Pancreatic Neuroendocrine Tumors (PNETs)


30 Sep 2019


Poster Discussion – NETs and endocrine tumours


Johan Botling


Annals of Oncology (2019) 30 (suppl_5): v564-v573. 10.1093/annonc/mdz256


J. Botling1, A. Lamarca2, D. Bajic3, O. Norlen4, V. Lönngren1, J. Kjaer4, B. Eriksson3, S. Welin3, P. Hellman4, G. Rindi5, B. Skogseid3, J. Crona3

Author affiliations

  • 1 Department Of Immunology, Genetics And Pathology, Uppsala University, 75185 - Uppsala/SE
  • 2 Medical Oncology / Institute Of Cancer Sciences, The Christie NHS Foundation Trust / University of Manchester, M20 4BX - Manchester/GB
  • 3 Department Of Medical Sciences, Uppsala University, 75185 - Uppsala/SE
  • 4 Department Of Surgical Sciences, Uppsala University, 75185 - Uppsala/SE
  • 5 Institute Of Anatomic Pathology, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, 00168 - Roma/IT


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Abstract 1590


Tumor proliferation and grade are important prognostic factors at diagnosis of PNETs. Little is known about how these factors change over time and if longitudinal increase in Ki67-index is associated with prognosis. The purpose of this work was to describe longitudinal changes in Ki67-index and tumor grade, as well as its impact on overall survival, in PNETs.


Platelet free plasma from 68 GEP-NET patients was collected. Whole miRNOME NGS analysis was performed on exome enriched small-RNAs fraction of 24 patients: 12 18PET/FDG+ and 12 18PET/FDG-. MiRNAs significantly associated with 18PET/FDG outcome has been identified and validated by RT/qPCR on overall case series. Target miRNAs fold enrichment were then combined to create predictors (pAB, pAC, pBC and pABC). Man-Whitney test was applied and validated target miRNAs had been correlated with clinical outcome and clinical parameters (ki-67, grading, tumor burden and 68Gallium-PET SUVmax).


NGS whole miRNOME analysis revealed 10 target miRNAs able to distinguish 18FDG/PET positive from negative Pancreatic-NETs (PNETs). Subsequently, mir-A, mir-B, mir-C (patent pending) have been validated on overall case series by multiplex RT/qPCR (p < 0,0047 and p < 0,0001, respectively), on PNETs case series and pBC and pABC resulted to be the best predictors (p < 0,0001). All validated miRNAs and derived predictors, especially mir-B, result significantly increased in small intestine (SINETs) and in PNETs patients when compared to healthy controls. Correlation analysis between target miRNAs and clinical parameters also revealed that mir-B negatively correlates with 68Ga-PET SUVmax (p < 0,04), suggesting interference with SSTR expression.


We defined a 3 miRNAs signature able to correlate with 18FDG/PET status. Over expression of mir-A, mir-B, mir-C or combined predictors in PNETs can provide prognostic information on tumor aggressiveness and might help to identify PRRT non-responders. In addition mir-B negatively correlates with clinical outcome and 68Ga-PET SUVmax. We are investigating if mirB interfere with SSTR expression, affecting PRRT efficacy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Uppsala University.


European Neuroendocrine Tumor Society, Uppsala University.


J. Botling: Honoraria (self): Novartis. A. Lamarca: Honoraria (self): Merck; Honoraria (self): Pfizer; Honoraria (self): Ipsen; Advisory / Consultancy: EISAI; Advisory / Consultancy: Nutricia; Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Bayer; Travel / Accommodation / Expenses: AAA; Travel / Accommodation / Expenses: SirtEx; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Mylan; Travel / Accommodation / Expenses: Delcath. G. Rindi: Honoraria (self): Novartis; Honoraria (self): Ipsen. J. Crona: Honoraria (self): Novartis; Honoraria (self): Ipsen. All other authors have declared no conflicts of interest.

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