Primary renal well-differentiated neuroendocrine tumour (carcinoid): next-generation sequencing study of 11 cases

Pivovarcikova K, Agaimy A, Martinek P, Alaghehbandan R, Perez-Montiel D, Alvarado-Cabrero I, Rogala J, Kuroda N, Rychly B, Gasparov S, Michalova K, Michal M, Hora M, Pitra T, Tuckova I, Laciok S, Mareckova J, Hes O (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Histopathology Wiley

Book Volume: 75

Pages Range: 104-117

Journal Issue: 1

DOI: 10.1111/his.13856

Abstract

Aims: Primary renal well-differentiated neuroendocrine tumour (NET) (hereafter referred to as renal NET) is rare, with ~100 cases having been reported in the literature. There are also limited data on the molecular–genetic background of primary renal NETs. Methods and results: We analysed 11 renal NETs by using next-generation sequencing (NGS) to identify characteristic genetic aberrations. All tumours were positive for synaptophysin, and also expressed insulinoma-associated protein 1 (10/11), chromogranin-A (8/11), and CD56 (3/11). Cytoplasmic positivity of CD99 was present in eight of 11 cases, and strong nuclear expression of α-thalassaemia/mental retardation syndrome X-linked (ATRX) was retained in all 11 cases. Molecular–genetic analysis of aberration of VHL gave negative results in all cases. Loss of heterozygosity on chromosome 3p21 was found in three of nine analysable cases. NGS was successful in nine cases, showing a total of 56 variants being left after the updated filtering process, representing an average of five variants per sample. All analysable cases were negative for ATRX and DAXX (death-domain associated protein X) mutations. The most frequently mutated genes were CDH1 and TET2, with three mutations in two cases. Mutations in AKT3, ROS1, PIK3R2, BCR and MYC were found in two cases. The remaining 41 genes were found to be mutated only in individual cases. In four cases, the mutations affected a subset of genes related to angiogenesis. Conclusions: Overall, the mutation profile of primary renal NETs is variable, and none of the studied genes or affected pathways seems to be specific for renal NET.

Authors with CRIS profile

Abbas Agaimy Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie

Involved external institutions

National Autonomous University of Mexico / Universidad Nacional Autónoma de México (UNAM) MX Mexico (MX) Univerzita Karlova v Praze / Charles University in Prague CZ Czech Republic (CZ) University of Zagreb / Sveučilište u Zagrebu HR Croatia (HR) Military University Hospital Prague / Ústřední vojenská nemocnice CZ Czech Republic (CZ) Instituto Nacional de Cancerología MX Mexico (MX) University of British Columbia CA Canada (CA) Japanese Red Cross Kochi Hospital JP Japan (JP)

How to cite

APA:

Pivovarcikova, K., Agaimy, A., Martinek, P., Alaghehbandan, R., Perez-Montiel, D., Alvarado-Cabrero, I.,... Hes, O. (2019). Primary renal well-differentiated neuroendocrine tumour (carcinoid): next-generation sequencing study of 11 cases. Histopathology, 75(1), 104-117. https://dx.doi.org/10.1111/his.13856

MLA:

Pivovarcikova, Kristyna, et al. "Primary renal well-differentiated neuroendocrine tumour (carcinoid): next-generation sequencing study of 11 cases." Histopathology 75.1 (2019): 104-117.

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