Evidence map›Paper›PMID 34108644›Full record

ArticleProstate cancer and prostatic diseases2021

MSH2-deficient prostate tumours have a distinct immune response and clinical outcome compared to MSH2-deficient colorectal or endometrial cancer.

Patrick McCoy, Stefano Mangiola, Geoff Macintyre, Ryan Hutchinson, Ben Tran, Bernard Pope, Peter Georgeson, Matthew K H Hong, Natalie Kurganovs, Sebastian Lunke and 10 more

Abstract read
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In one paragraph

Article in Prostate cancer and prostatic diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.0field-weighted citation impact, top 23% of its field
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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 11 citations in OpenAlex.

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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

20 authors at 7 institutions in 4 countries.

Patrick McCoyDepartments of Surgery and Urology, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, Australia. patrickjmccoy@bigpond.com.ORCID http://orcid.org/0000-0001-9412-110X
Stefano MangiolaDepartments of Surgery and Urology, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, Australia.ORCID http://orcid.org/0000-0001-7474-836X
Geoff MacintyreStatistics and Computational Biology Group, Cambridge, UK.
Ryan HutchinsonWalter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
Ben TranWalter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
Bernard PopeColorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, VIC, Australia.ORCID http://orcid.org/0000-0002-4840-1095
Peter GeorgesonColorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, VIC, Australia.ORCID http://orcid.org/0000-0002-5096-4735
Matthew K H HongDepartments of Surgery and Urology, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, Australia.ORCID http://orcid.org/0000-0002-0727-2848
Natalie KurganovsDepartments of Surgery and Urology, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, Australia.
Sebastian LunkeDepartment of Pathology, University of Melbourne, Parkville, VIC, Australia.
Michael J ClarksonDepartments of Surgery and Urology, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, Australia.
Marek CmeroDepartments of Surgery and Urology, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, Australia.ORCID http://orcid.org/0000-0001-7783-5530
Michael KergerAustralian Prostate Cancer Research Centre, Melbourne, VIC, Australia.
Ryan StuchberyAustralian Prostate Cancer Research Centre, Melbourne, VIC, Australia.
Ken ChowDepartments of Surgery and Urology, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, Australia.ORCID http://orcid.org/0000-0001-5904-2684
Izhak HavivFaculty of Medicine in the Galilee, Bar Ilan University, Ramat Gan, Israel.
Andrew RyanTissuPath Specialist Pathology, Mount Waverley, Melbourne, VIC, Australia.
Anthony J CostelloDepartments of Surgery and Urology, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, Australia.
Niall M CorcoranDepartments of Surgery and Urology, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, Australia.
Christopher M HovensDepartments of Surgery and Urology, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, Australia.
The Royal Melbourne Hospital · AUProstate Cancer Foundation of Australia · AUThe University of Melbourne · AUBar-Ilan University · ILOntario Institute for Cancer Research · CATissuPath · AUWalter and Eliza Hall Institute of Medical Research · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRecent publications have shown patients with defects in the DNA mismatch repair (MMR) pathway driven by either MSH2 or MSH6 loss experience a significant increase in the incidence of prostate cancer. Moreover, this increased incidence of prostate cancer is accompanied by rapid disease progression and poor clinical outcomes. METHODS AND

resultsWe show that androgen-receptor activation, a key driver of prostate carcinogenesis, can disrupt the MSH2 gene in prostate cancer. We screened tumours from two cohorts (recurrent/non-recurrent) of prostate cancer patients to confirm the loss of MSH2 protein expression and identified decreased MSH2 expression in recurrent cases. Stratifying the independent TCGA prostate cancer cohort for MSH2/6 expression revealed that patients with lower levels of MSH2/6 had significant worse outcomes, in contrast, endometrial and colorectal cancer patients with lower MSH2/6 levels. MMRd endometrial and colorectal tumours showed the expected increase in mutational burden, microsatellite instability and enhanced immune cell mobilisation but this was not evident in prostate tumours.

conclusionsWe have shown that loss or reduced levels of MSH2/MSH6 protein in prostate cancer is associated with poor outcome. However, our data indicate that this is not associated with a statistically significant increase in mutational burden, microsatellite instability or immune cell mobilisation in a cohort of primary prostate cancers.

Indexed as

Colorectal NeoplasmsDNA Mismatch RepairEndometrial NeoplasmsFemaleGene RearrangementGerm-Line MutationHumansMaleMicrosatellite InstabilityMutS Homolog 2 ProteinProstatic NeoplasmsTranscriptomeTumor Cells, CulturedWhole Genome SequencingMSH2 protein, humanMutS Homolog 2 Protein

Identifiers

PMID34108644
OpenAlexW3170529387

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

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.