Evidence map›Paper›PMID 30555044›Full record

Trial reportEBioMedicine2019

Molecular profiling of longitudinally observed small colorectal polyps: A cohort study.

M C J van Lanschot, B Carvalho, C Rausch, P Snaebjornsson, M van Engeland, E J Kuipers, J Stoker, C J Tutein Nolthenius, E Dekker, G A Meijer

Open access · goldAbstract readMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in EBioMedicine, 2019. 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 24% 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, 15 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. CpG Island Methylator Phenotype-A Hope for the Future or a Road to Nowhere?International journal of molecular sciences · 2022
    Review
  7. Article
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

10 authors at 4 institutions in 1 country.

M C J van LanschotDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands; Cancer Centre Amsterdam, Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
B CarvalhoDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
C RauschDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
P SnaebjornssonDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
M van EngelandDepartment of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands.
E J KuipersDepartment of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus University Medical Centre, Rotterdam, the Netherlands.
J StokerDepartment of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
C J Tutein NoltheniusDepartment of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
E DekkerCancer Centre Amsterdam, Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
G A MeijerDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands. Electronic address: g.meijer@nki.nl.
The Netherlands Cancer Institute · NLUniversity of Amsterdam · NLErasmus University Rotterdam · NLMaastricht University · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundKnowledge of the natural history of colorectal adenomas is limited because these lesions are removed upon detection. The few studies in which small adenomas have been left in situ for a limited period of time, have shown that most lesions remain stable or even completely regress. Specific DNA copy number changes ('cancer associated events' or CAEs) are associated with progression of adenomas to cancer. In this study we evaluated whether molecular features of progression correlated with growth of small polyps.

methodsSmall (6-9 mm) colorectal precursor lesions detected on CT-colonography (CTC) were left in situ and re-evaluated with CTC after three years. Based on volumetric change, polyps were classified as either grown, stable or regressed. Surveillance CTC was followed by colonoscopy, during which all lesions were resected. Using DNA isolated from FFPE polyp tissues, low-coverage whole genome sequencing was performed to determine DNA copy number profiles, as well as target enrichment mutation analysis and CpG island methylation phenotype (CIMP) analysis. Expression of DNA mismatch repair (MMR) proteins was determined by immunohistochemistry. Samples were marked as MMR proficient if all MMR proteins were expressed.

findingsOut of 68 polyps resected at colonoscopy, for 65 (96%) material was available. Of these, 31 (48%) had grown, 27 (41%) remained stable and 7 (11%) regressed. Polyps with at least one CAE had higher growth rates compared to polyps without CAEs (difference 91% growth (95% CI 13-169), p = .023). CAEs were absent in lesions that had partially regressed. Mutations occurred in 94% of the polyps, with higher growth rates being associated with polyps having ≥2 mutations compared to lesions with only 0-1 mutations (difference 99% growth (95% CI 9-189), p = .032). All samples were MMR proficient. No relation between growth and CIMP was observed.

interpretationMolecular alterations associated with colorectal cancer, correlated with growth of small polyps and were absent in polyps that regressed. Therefore, this longitudinal study provides in vivo support in the human setting for the functional role of these molecular alterations, that have mostly been identified by cross sectional observations in tissue samples of colorectal adenomas and cancers. FUND: Alpe d'Huzes- Dutch Cancer Society (project number NKI2013-6338).

Indexed as

DNA Copy Number VariationsMutationAgedColonic PolypsColonography, Computed TomographicCross-Sectional StudiesDNA-Binding ProteinsDNA Mismatch RepairFemaleHumansLongitudinal StudiesMaleMiddle AgedMismatch Repair Endonuclease PMS2MutL Protein Homolog 1MutS Homolog 2 ProteinDNA-Binding ProteinsG-T mismatch-binding proteinMismatch Repair Endonuclease PMS2MLH1 protein, humanMSH2 protein, humanMutL Protein Homolog 1MutS Homolog 2 ProteinPMS2 protein, humanColorectal polypsGrowthMolecular profilingNatural behaviour

Identifiers

PMID30555044
PMCPMC6354708
OpenAlexW2905518067

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.