Evidence map›Paper›PMID 31677491›Full record

ArticleTranslational oncology2019

Elevated Microsatellite Alterations at Selected Tetranucleotides (EMAST) Is Not Attributed to MSH3 Loss in Stage I-III Colon cancer: An Automated, Digitalized Assessment by Immunohistochemistry of Whole Slides and Hot Spots.

Martin M Watson, Dordi Lea, Hanne R Hagland, Kjetil Søreide

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01762813 (Prospective, Population-based Cohort Collection of Blood Samples and Tumor Tissue From Patients Operated on for Primary or Metastatic Colorectal Cancer), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 25% 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.

NCT01762813 recruitingnot on this map

Prospective, Population-based Cohort Collection of Blood Samples and Tumor Tissue From Patients Operated on for Primary or Metastatic Colorectal Cancer

TypeobservationalSponsorHelse Stavanger HFRan2013 to 2036Enrolled1,200ConditionsColorectal CancerArmsopen and laparoscopic surgery
3 · Its place in the literature

Who cites it

5 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

4 authors at 3 institutions in 1 country.

Martin M WatsonGastrointestinal Translational Research Unit, Laboratory for Molecular Medicine, Stavanger University Hospital, Gerd Ragna Bloch Thorsens Gate 8, 4011, Stavanger, Norway; Department of Gastrointestinal Surgery, Stavanger University Hospital, Gerd Ragna Bloch Thorsens Gate 8, 4011, Stavanger, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway. Electronic address: martin.watson@uib.no.
Dordi LeaGastrointestinal Translational Research Unit, Laboratory for Molecular Medicine, Stavanger University Hospital, Gerd Ragna Bloch Thorsens Gate 8, 4011, Stavanger, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Pathology, Stavanger University Hospital, Gerd Ragna Bloch Thorsens Gate 8, 4011, Stavanger, Norway.
Hanne R HaglandGastrointestinal Translational Research Unit, Laboratory for Molecular Medicine, Stavanger University Hospital, Gerd Ragna Bloch Thorsens Gate 8, 4011, Stavanger, Norway; Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Norway.
Kjetil SøreideGastrointestinal Translational Research Unit, Laboratory for Molecular Medicine, Stavanger University Hospital, Gerd Ragna Bloch Thorsens Gate 8, 4011, Stavanger, Norway; Department of Gastrointestinal Surgery, Stavanger University Hospital, Gerd Ragna Bloch Thorsens Gate 8, 4011, Stavanger, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.
Stavanger University Hospital · NOUniversity of Bergen · NOUniversity of Stavanger · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionEMAST is a poorly understood form of microsatellite instability (MSI) in colorectal cancer (CRC) for which loss of MSH3 has been proposed as the underlying mechanism, based on experimental studies. We aimed to evaluate whether MSH3 loss is associated with EMAST in CRC.

methodsA consecutive cohort of patients with stage I-III CRC. Digital image analysis using heatmap-derived hot spots investigated MSH3 expression by immunohistochemistry. Fragment analysis of multiplex PCR was used to assess MSI and EMAST, and results cross-examined with MSH3 protein expression.

resultsOf 152 patients, EMAST was found in 50 (33%) and exclusively in the colon. Most EMAST-positive cancers had instability at all 5 markers, and EMAST overlapped with MSI-H in 42/50 cases (84%). The most frequently altered tetranucleotide markers were D8S321 (38.2% of tumors) and D20S82 (34.4%). Subjective evaluation of MSH3 expression by IHC in tumor found ≤10% negative tumor cells in all samples, most being ≤5% negative. Digital analysis improved the detection but showed a similar spread of MSH3 loss (range 0.1-15.7%, mean 2.2%). Hotspot MSH3 negativity ranged between 0.1 to 95.0%, (mean 8.6%) with significant correlation with the whole slide analysis (Spearman's rho=0.677 P<.001). Loss of MSH3 expression did not correlate with EMAST.

conclusionsIn a well-defined cohort of patients with CRC, loss of MSH3 was not associated with EMAST. Further investigation into the mechanisms leading to EMAST in CRC is needed.

Identifiers

PMID31677491
PMCPMC6930943
OpenAlexW2988951891

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Registered trials

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.