ImmunoMembrane: a publicly available web application for digital image analysis of HER2 immunohistochemistry

Tuominen, Vilppu J.; Tolonen, Teemu; Isola, Jorma

doi:10.1111/j.1365-2559.2011.04142.x

Cited by 72 publications

(57 citation statements)

References 15 publications

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“…Evaluation of Immunohistochemical Staining-EGFR, HER2, and HER3 immunohistochemical staining was quantified using the program ImmunoMembrane (Institute of Biomedical Technology, Finland), which classified images into three categories, 0/1ϩ, 2ϩ, or 3ϩ, based on the membrane staining completeness and intensity (42). This classification took into account segments of 3,3Ј-diaminobenzidine-stained membrane, and a score was calculated by averaging images of three random fields for each sample.…”

Section: Methodsmentioning

confidence: 99%

The Metastasis Suppressor, N-MYC Downstream-regulated Gene-1 (NDRG1), Down-regulates the ErbB Family of Receptors to Inhibit Downstream Oncogenic Signaling Pathways

Kovačević

Menezes

Sahni

et al. 2016

Journal of Biological Chemistry

113

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N-MYC downstream-regulated gene-1 (NDRG1) is a potent growth and metastasis suppressor that acts through its inhibitory effects on a wide variety of cellular signaling pathways, including the TGF-␤ pathway, protein kinase B (AKT)/PI3K pathway, RAS, etc. To investigate the hypothesis that its multiple effects could be regulated by a common upstream effector, the role of NDRG1 on the epidermal growth factor receptor (EGFR) and other members of the ErbB family, namely human epidermal growth factor receptor 2 (HER2) and human epidermal growth factor receptor 3 (HER3), was examined. We demonstrate that NDRG1 markedly decreased the expression and activation of EGFR, HER2, and HER3 in response to the epidermal growth factor (EGF) ligand, while also inhibiting formation of the EGFR/HER2 and HER2/HER3 heterodimers. In addition, NDRG1 also decreased activation of the downstream MAPKK in response to EGF. Moreover, novel anti-tumor agents of the di-2-pyridylketone class of thiosemicarbazones, namely di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone and di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone, which markedly up-regulate NDRG1, were found to inhibit EGFR, HER2, and HER3 expression and phosphorylation in cancer cells. However, the mechanism involved appeared dependent on NDRG1 for di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone, but was independent of this metastasis suppressor for di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone. This observation demonstrates that small structural changes in thiosemicarbazones result in marked alterations in molecular targeting. Collectively, these results reveal a mechanism for the extensive downstream effects on cellular signaling attributed to NDRG1. Furthermore, this study identifies a novel approach for the treatment of tumors resistant to traditional EGFR inhibitors.

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Section: Methodsmentioning

confidence: 99%

The Metastasis Suppressor, N-MYC Downstream-regulated Gene-1 (NDRG1), Down-regulates the ErbB Family of Receptors to Inhibit Downstream Oncogenic Signaling Pathways

Kovačević

Menezes

Sahni

et al. 2016

Journal of Biological Chemistry

113

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“…HER2 tissue stain intensity was evaluated by using the Immunomembrane plugin for Image J, as previously described. 15,18 Stain intensity in this program is quantified on a relative 0 to 10 scale. Estrogen receptor/PR stain intensity was evaluated by using Image Pro Premier (Media Cybernetics, Rockville, Maryland), as previously described.…”

Section: Image and Data Acquisition And Analysismentioning

confidence: 99%

“…This is conceptually similar to the Immunomembrane and ImmunoRatio software tools that are provided by the Institute of Biomedical Technology, University of Tampere, Finland. 1,18 This approach provides participating laboratories with all of the tools to perform their own analytic response curve.…”

mentioning

confidence: 99%

Quantitative Assessment of Immunohistochemistry Laboratory Performance by Measuring Analytic Response Curves and Limits of Detection

Sompuram¹,

Vani²,

Schaedle³

et al. 2018

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Numerous studies highlight interlaboratory performance variability in diagnostic immunohistochemistry (IHC) testing. Despite substantial improvements over the years, the inability to quantitatively and objectively assess immunostain sensitivity complicates interlaboratory standardization.Objective.-To quantitatively and objectively assess the sensitivity of the immunohistochemical stains for human epidermal growth factor receptor type 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) across IHC laboratories in a proficiency testing format. We measure sensitivity with parameters that are new to the field of diagnostic IHC: analytic response curves and limits of detection.Design.-Thirty-nine diagnostic IHC laboratories stained a set of 3 slides, one each for HER2, ER, and PR. Each slide incorporated a positive tissue section and IHControls at 5 different concentrations. The IHControls comprise cell-sized clear microbeads coated with defined concentrations of analyte (HER2, ER, and/or PR). The laboratories identified the limits of detection and then mailed the slides for quantitative assessment.Results.-Each commercial immunostain demonstrated a characteristic analytic response curve, reflecting strong reproducibility among IHC laboratories using the same automation and reagents prepared per current Good Manufacturing Practices. However, when comparing different commercial vendors (using different reagents), the data reveal up to 100-fold differences in analytic sensitivity. For proficiency testing purposes, quantitative assessment using analytic response curves was superior to subjective interpretation of limits of detection.Conclusions.-Assessment of IHC laboratory performance by quantitative measurement of analytic response curves is a powerful, objective tool for identifying outlier IHC laboratories. It uniquely evaluates immunostain performance across a range of defined analyte concentrations.

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“…The burgeoning field of digital pathology has steered the development of automated image analysis systems as diagnostic accompaniment to pathologists [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Histopathology image analysis systems, when robustly designed, are attractive because they can provide diagnostic measurements which are reproducible.…”

Section: Introductionmentioning

confidence: 99%

“…In the implementation of a histopathology image analysis system, the colors of the stained tissue components are often considered as their segmentation or classification feature [4][5][6][7][8][9][10][11][12][13]. The issue in utilizing color for histopathology image analysis arises when the staining conditions of test and training images differ.…”

Section: Introductionmentioning

confidence: 99%

Staining Correction in Digital Pathology by Utilizing a Dye Amount Table

Bautista

Yagi

2015

J Digit Imaging

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The stained colors of the tissue components are popularly used as features for image analysis. However, variations in the staining condition of the histology slides prompt variations to the color distribution of the stained tissue samples which could impact the accuracy of the analysis. In this paper, we present a method to correct the staining condition of a histology image. In the method, a look-up table (LUT) based on the dye amounts absorbed by the sample is built. The LUT can be built when either (i) the source and reference staining conditions are specified or (ii) when the user simply wants to recreate his/her preferred staining condition without specifying any reference slide. The effectiveness of the present method was evaluated in two aspects: (i) CIELAB color difference of nuclei, cytoplasm, and red blood cells, between the ten different slides of liver tissue, and (ii) classification of the different tissue components. Application of the present staining correction method reduced the color difference between the slides by an average factor of 9.8 and the classification performance of a linear discriminant classifier improved by 16.5 % on the average. Results of the paired t test statistical analysis further showed that the reduction in the CIELAB color difference between the slides and the improvement in the classifier's performance when staining correction was implemented is significant at p<0.001.

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ImmunoMembrane: a publicly available web application for digital image analysis of HER2 immunohistochemistry

Abstract: We anticipate that publicly available web applications, such as ImmunoMembrane, will accelerate the adoption of automated image analysis in clinical diagnostics of HER2 IHC. ImmunoMembrane is freely accessible at: http://jvsmicroscope.uta.fi/immunomembrane/.

Cited by 72 publications

References 15 publications

The Metastasis Suppressor, N-MYC Downstream-regulated Gene-1 (NDRG1), Down-regulates the ErbB Family of Receptors to Inhibit Downstream Oncogenic Signaling Pathways

The Metastasis Suppressor, N-MYC Downstream-regulated Gene-1 (NDRG1), Down-regulates the ErbB Family of Receptors to Inhibit Downstream Oncogenic Signaling Pathways

Quantitative Assessment of Immunohistochemistry Laboratory Performance by Measuring Analytic Response Curves and Limits of Detection

Staining Correction in Digital Pathology by Utilizing a Dye Amount Table

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