Evidence map›Paper›PMID 27583442›Full record

ArticlePloS one2016

Development and Validation of a Histological Method to Measure Microvessel Density in Whole-Slide Images of Cancer Tissue.

Koen M Marien, Valerie Croons, Yannick Waumans, Ellen Sluydts, Stefanie De Schepper, Luc Andries, Wim Waelput, Erik Fransen, Peter B Vermeulen, Mark M Kockx and 1 more

Abstract readValidation Study
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing 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

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

36 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.

Koen M MarienDivision of Physiopharmacology, University of Antwerp, Antwerp, Belgium.ORCID http://orcid.org/0000-0001-7212-7682
Valerie CroonsHistoGeneX NV, Antwerp, Belgium.
Yannick WaumansHistoGeneX NV, Antwerp, Belgium.
Ellen SluydtsHistoGeneX NV, Antwerp, Belgium.
Stefanie De SchepperHistoGeneX NV, Antwerp, Belgium.
Luc AndriesHistoGeneX NV, Antwerp, Belgium.
Wim WaelputDepartment of Pathology, University Hospital Brussels (UZ Brussel), Brussels, Belgium.
Erik FransenStatUa Center for Statistics, University of Antwerp, Antwerp, Belgium.
Peter B VermeulenCORE (Translational Cancer Research Unit, GZA Hospitals), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
Mark M KockxHistoGeneX NV, Antwerp, Belgium.
Guido R Y De MeyerDivision of Physiopharmacology, University of Antwerp, Antwerp, Belgium.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite all efforts made to develop predictive biomarkers for antiangiogenic therapies, no unambiguous markers have been identified so far. This is due to among others the lack of standardized tests. This study presents an improved microvessel density quantification method in tumor tissue based on stereological principles and using whole-slide images. Vessels in tissue sections of different cancer types were stained for CD31 by an automated and validated immunohistochemical staining method. The stained slides were digitized with a digital slide scanner. Systematic, uniform, random sampling of the regions of interest on the whole-slide images was performed semi-automatically with the previously published applications AutoTag and AutoSnap. Subsequently, an unbiased counting grid was combined with the images generated with these scripts. Up to six independent observers counted microvessels in up to four cancer types: colorectal carcinoma, glioblastoma multiforme, ovarian carcinoma and renal cell carcinoma. At first, inter-observer variability was found to be unacceptable. However, after a series of consensus training sessions and interim statistical analysis, counting rules were modified and inter-observer concordance improved considerably. Every CD31-positive object was counted, with exclusion of suspected CD31-positive monocytes, macrophages and tumor cells. Furthermore, if interconnected, stained objects were considered a single vessel. Ten regions of interest were sufficient for accurate microvessel density measurements. Intra-observer and inter-observer variability were low (intraclass correlation coefficient > 0.7) if the observers were adequately trained.

Indexed as

Blood VesselsHumansNeoplasmsNeovascularization, PathologicObserver VariationPlatelet Endothelial Cell Adhesion Molecule-1Reproducibility of ResultsPlatelet Endothelial Cell Adhesion Molecule-1

Identifiers

PMID27583442
PMCPMC5008750

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Registered trials

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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.