Poster Discussion – NETs and endocrine tumours Poster Discussion session

1386PD - Longitudinal increase in Ki67 and high-grade transformation in pancreatic neuroendocrine tumours (PNETs) (ID 1590)

Presentation Number
1386PD
Lecture Time
10:50 - 10:50
Speakers
  • Johan Botling (Uppsala, Sweden)
Session Name
Poster Discussion – NETs and endocrine tumours
Location
Cartagena Auditorium (Hall 3), Fira Gran Via, Barcelona, Spain
Date
30.09.2019
Time
10:30 - 11:30

Abstract

Background

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.

Methods

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).

Results

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.

Conclusions

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.

Legal entity responsible for the study

Uppsala University.

Funding

European Neuroendocrine Tumor Society, Uppsala University.

Disclosure

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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