ImmunoRatio: a publicly available web application for quantitative image analysis of estrogen receptor (ER), progesterone receptor (PR), and Ki-67

By Vilppu J. Tuominen, Sanna Ruotoistenmäki, Arttu Viitanen, Mervi Jumppanen, J. Isola. Breast Cancer Research, 2010

493 citations recorded by the source corpus.

IntroductionAccurate assessment of estrogen receptor (ER), progesterone receptor (PR), and Ki-67 is essential in the histopathologic diagnostics of breast cancer. Commercially available image analysis systems are usually bundled with dedicated analysis hardware and, to our knowledge, no easily installable, free software for immunostained slide scoring has been described. In this study, we describe a free, Internet-based web application for quantitative image analysis of ER, PR, and Ki-67 immunohistochemistry in breast cancer tissue sections.MethodsThe application, named ImmunoRatio, calculates the percentage of positively stained nuclear area (labeling index) by using a color deconvolution algorithm for separating the staining components (diaminobenzidine and hematoxylin) and adaptive thresholding for nuclear area segmentation. ImmunoRatio was calibrated using cell counts defined visually as the gold standard (training set, n = 50). Validation was done using a separate set of 50 ER, PR, and Ki-67 stained slides (test set, n = 50). In addition, Ki-67 labeling indexes determined by ImmunoRatio were studied for their prognostic value in a retrospective cohort of 123 breast cancer patients.ResultsThe labeling indexes by calibrated ImmunoRatio analyses correlated well with those defined visually in the test set (correlation coefficient r = 0.98). Using the median Ki-67 labeling index (20%) as a cutoff, a hazard ratio of 2.2 was obtained in the survival analysis (n = 123, P = 0.01). ImmunoRatio was shown to adapt to various staining protocols, microscope setups, digital camera models, and image acquisition settings. The application can be used directly with web browsers running on modern operating systems (e.g., Microsoft Windows, Linux distributions, and Mac OS). No software downloads or installations are required. ImmunoRatio is open source software, and the web application is publicly accessible on our website.ConclusionsWe anticipate that free web applications, such as ImmunoRatio, will make the quantitative image analysis of ER, PR, and Ki-67 easy and straightforward in the diagnostic assessment of breast cancer specimens.

Subfields: Artificial Intelligence, Biophysics, Cancer Research

View Paper: https://www.semanticscholar.org/paper/db6d8a2dc65831ecce9bfd7dd584e036e47c8132

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In Artificial Intelligence

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Citations in the corpus

• Breast Cancer Histopathology Image Analysis: A Review (2014, unknown): “Two publicly available web applications for ER/PR and HER2 quantifications are described in [28] and [35].”
• Breast cancer stem cell markers CD44, CD24 and ALDH1: expression distribution within intrinsic molecular subtype (2011, methodology): “10 The quanti fi cation of cell proliferation by Ki67 expression was measured using the publicly available web application software ImunoRatio, as recently described by Tuominen et al , 39 and validated by a breast cancer pathologist.”
• IHC Profiler: An Open Source Plugin for the Quantitative Evaluation and Automated Scoring of Immunohistochemistry Images of Human Tissue Samples (2014, methodology): “…source and widely used digital image analysis program ImageJ unlike a few tools that require a separate platform to perform the desired operation [5,11]; ii. requires only the sample image photographs and returns a full pixel analysis report of the entire image area; iii. eliminates inter-observer…”
• Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update. (2020, background): “The searches identified 4,897 abstracts, and ultimately, 87 papers met the selection criteria.(11,14-99) Articles were selected for inclusion in the systematic review of the evidence based on the following criteria:”