Evidence map›Paper›PMID 22515559›Full record

ArticleDiagnostic pathology2012

Quantitative comparison of immunohistochemical staining measured by digital image analysis versus pathologist visual scoring.

Anthony E Rizzardi, Arthur T Johnson, Rachel Isaksson Vogel, Stefan E Pambuccian, Jonathan Henriksen, Amy Pn Skubitz, Gregory J Metzger, Stephen C Schmechel

Open access · goldAbstract readComparative Study
In one paragraph

Article in Diagnostic pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 218 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
218citing papers in PubMed, 2 pooled it
38.4field-weighted citation impact, top 1% 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

218 citing papers in PubMed, 2 syntheses or guidelines pooled it, 430 citations in OpenAlex.

  1. Pooled it
  2. State-of-the-Art on Wound Vitality Evaluation: A Systematic Review.International journal of molecular sciences · 2022
    Pooled it
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  19. Digital pathology in tau research: A comparison of QuPath and HALO.Journal of neuropathology and experimental neurology · 2025
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158 more citing papers are in PubMed but not listed here.

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

8 authors at 2 institutions in 1 country.

Anthony E RizzardiDepartment of Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street SE, MMC76, Minneapolis, MN 55455, USA.
Arthur T Johnson
Rachel Isaksson Vogel
Stefan E Pambuccian
Jonathan Henriksen
Amy Pn Skubitz
Gregory J Metzger
Stephen C Schmechel
University of Minnesota · USUniversity of Minnesota Medical Center · US

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Douglas Yee · 1998 to 2026
$100.4M
Virological Measurements of Cryptic ReplicationP01AI074340 · NIAID · UNIVERSITY OF MINNESOTA · PI SCHACKER, TIMOTHY W · 2008 to 2012
$12.1M
UAB / UMN SPORE in Pancreatic CancerP50CA101955 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BUCHSBAUM, DONALD J · 2010 to 2014
$11.1M
Antifibrotic Therapy to Improve Immune reconstitution in HIVR01AI093319 · NIAID · UNIVERSITY OF MINNESOTA · PI SCHACKER, TIMOTHY W · 2011 to 2014
$2.8M
Multi-parametric MRI Determination of Prostate Cancer Aggressiveness and ExtentR01CA131013 · NCI · UNIVERSITY OF MINNESOTA · PI METZGER, GREGORY JOHN · 2008 to 2012
$1.6M
Biomarkers with Biological Function in Ovarian CarcinomaR01CA106878 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI SKUBITZ, AMY PATRICE · 2005 to 2009
$1.4M
University of Minnesota Clinical and Translational Science Institute (UMN CTSI)KL2RR033182 · NCRR · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R · 2011 to 2011
$1.4M
NCI NIH HHS P30-CA77598NCI NIH HHS P50-CA101955NCI NIH HHS R01-CA106878NCI NIH HHS R01 CA131013NCI NIH HHS R01-CA131013NCRR NIH HHS KL2-RR033182NIAID NIH HHS P01-AI074340NIAID NIH HHS R01-AI093319
6 · The paper itself

Abstract

Immunohistochemical (IHC) assays performed on formalin-fixed paraffin-embedded (FFPE) tissue sections traditionally have been semi-quantified by pathologist visual scoring of staining. IHC is useful for validating biomarkers discovered through genomics methods as large clinical repositories of FFPE specimens support the construction of tissue microarrays (TMAs) for high throughput studies. Due to the ubiquitous availability of IHC techniques in clinical laboratories, validated IHC biomarkers may be translated readily into clinical use. However, the method of pathologist semi-quantification is costly, inherently subjective, and produces ordinal rather than continuous variable data. Computer-aided analysis of digitized whole slide images may overcome these limitations. Using TMAs representing 215 ovarian serous carcinoma specimens stained for S100A1, we assessed the degree to which data obtained using computer-aided methods correlated with data obtained by pathologist visual scoring. To evaluate computer-aided image classification, IHC staining within pathologist annotated and software-classified areas of carcinoma were compared for each case. Two metrics for IHC staining were used: the percentage of carcinoma with S100A1 staining (%Pos), and the product of the staining intensity (optical density [OD] of staining) multiplied by the percentage of carcinoma with S100A1 staining (OD*%Pos). A comparison of the IHC staining data obtained from manual annotations and software-derived annotations showed strong agreement, indicating that software efficiently classifies carcinomatous areas within IHC slide images. Comparisons of IHC intensity data derived using pixel analysis software versus pathologist visual scoring demonstrated high Spearman correlations of 0.88 for %Pos (p < 0.0001) and 0.90 for OD*%Pos (p < 0.0001). This study demonstrated that computer-aided methods to classify image areas of interest (e.g., carcinomatous areas of tissue specimens) and quantify IHC staining intensity within those areas can produce highly similar data to visual evaluation by a pathologist. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1649068103671302.

Indexed as

AlgorithmsBiomarkers, TumorFemaleHumansImage Processing, Computer-AssistedImmunohistochemistryNeoplasms, Cystic, Mucinous, and SerousOvarian NeoplasmsPathology, ClinicalQuality ControlS100 ProteinsSoftwareStaining and LabelingBiomarkers, TumorS100A1 proteinS100 Proteins

Identifiers

PMID22515559
PMCPMC3379953
OpenAlexW2025623420

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.