Evidence map›Paper›PMID 38907236›Full record

ArticleDiagnostic pathology2024

Rare histologic transformation of a CTNNB1 (β-catenin) mutated prostate cancer with aggressive clinical course.

Dilara Akhoundova, Stefanie Fischer, Joanna Triscott, Marika Lehner, Phillip Thienger, Sina Maletti, Muriel Jacquet, Dinda S H Lubis, Lukas Bubendorf, Wolfram Jochum and 1 more

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In one paragraph

Article in Diagnostic pathology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Dilara AkhoundovaDepartment for BioMedical Research, University of Bern, Bern, 3008, Switzerland.
Stefanie FischerDepartment of Medical Oncology and Hematology, Cantonal Hospital St. Gallen, St. Gallen, 9007, Switzerland.
Joanna TriscottDepartment for BioMedical Research, University of Bern, Bern, 3008, Switzerland.
Marika LehnerDepartment for BioMedical Research, University of Bern, Bern, 3008, Switzerland.
Phillip ThiengerDepartment for BioMedical Research, University of Bern, Bern, 3008, Switzerland.
Sina MalettiDepartment for BioMedical Research, University of Bern, Bern, 3008, Switzerland.
Muriel JacquetDepartment for BioMedical Research, University of Bern, Bern, 3008, Switzerland.
Dinda S H LubisDepartment for BioMedical Research, University of Bern, Bern, 3008, Switzerland.
Lukas BubendorfInstitute of Medical Genetics and Pathology, University Hospital of Basel, Basel, 4031, Switzerland.
Wolfram JochumInstitute of Pathology, Cantonal Hospital St. Gallen, St. Gallen, 9007, Switzerland.
Mark A RubinDepartment for BioMedical Research, University of Bern, Bern, 3008, Switzerland. mark.rubin@unibe.ch.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCatenin (Cadherin-Associated Protein), Beta 1 (CTNNB1) genomic alterations are rare in prostate cancer (PCa). Gain-of-function mutations lead to overexpression of β-catenin, with consequent hyperactivation of the Wnt/β-catenin signaling pathway, implicated in PCa progression and treatment resistance. To date, successful targeted treatment options for Wnt/β-catenin - driven PCa are lacking.

methodsWe report a rare histologic transformation of a CTNNB1 (β-catenin) mutated metastatic castration resistant prostate cancer (mCRPC), clinically characterized by highly aggressive disease course. We histologically and molecularly characterized the liver metastatic tumor samples, as well as successfully generated patient-derived organoids (PDOs) and patient-derived xenograft (PDX) from a liver metastasis. We used the generated cell models for further molecular characterization and drug response assays.

resultsImmunohistochemistry of liver metastatic biopsies and PDX tumor showed lack of expression of typical PCa (e.g., AR, PSA, PSAP, ERG) or neuroendocrine markers (synaptophysin), compatible with double-negative CRPC, but was positive for nuclear β-catenin expression, keratin 7 and 34βE12. ERG rearrangement was confirmed by fluorescent in situ hybridization (FISH). Drug response assays confirmed, in line with the clinical disease course, lack of sensitivity to common drugs used in mCRPC (e.g., enzalutamide, docetaxel). The casein kinase 1 (CK1) inhibitor IC261 and the tankyrase 1/2 inhibitor G700-LK showed modest activity. Moreover, despite harbouring a CTNNB1 mutation, PDOs were largely insensitive to SMARCA2/4- targeting PROTAC degraders and inhibitor.

conclusionsThe reported CTNNB1-mutated mCRPC case highlights the potential challenges of double-negative CRPC diagnosis and underlines the relevance of further translational research to enable successful targeted treatment of rare molecular subtypes of mCRPC.

Indexed as

beta CateninMutationAgedAnimalsBiomarkers, TumorDisease ProgressionHumansLiver NeoplasmsMaleProstatic Neoplasms, Castration-Resistantbeta CateninBiomarkers, TumorCTNNB1 protein, humanCK1 inhibitorsCTNNB1 mutationHistologic transformationMetastatic castration-resistant prostate cancer (mCRPC)Prostate cancerTankyrase inhibitorsTargeted treatmentWnt/β-catenin pathway

Identifiers

PMID38907236
PMCPMC11191256

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.