Abstract

The method for nuclei segmentation in fluorescence in-situ hybridization (FISH) images, based on the inverse multifractal analysis (IMFA) is proposed. From the blue channel of the FISH image in RGB format, the matrix of Holder exponents, with one-by-one correspondence with the image pixels, is determined first. The following semi-automatic procedure is proposed: initial nuclei segmentation is performed automatically from the matrix of Holder exponents by applying predefined hard thresholding; then the user evaluates the result and is able to refine the segmentation by changing the threshold, if necessary. After successful nuclei segmentation, the HER2 (human epidermal growth factor receptor 2) scoring can be determined in usual way: by counting red and green dots within segmented nuclei, and finding their ratio. The IMFA segmentation method is tested over 100 clinical cases, evaluated by skilled pathologist. Testing results show that the new method has advantages compared to already reported methods.

Highlights

  • In developed countries the second cause of mortality is that of the cancer, just after the cardiovascular diseases as noted in World Health Organization (WHO) reports ( 2014)

  • According to the guidelines and recommendations stated from the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) (2013), the two FDA-approved methods for testing HER2 positivity are used in clinical praxis: the Immunohistochemistry (IHC) and In-situ hybridization (ISH)

  • Precise and detailed recommendations and guidelines for HER2 testing and scoring are given by ASCO/CAP (2013) and embedded in commercially available probe kits, for instance in HER2 fluorescence in-situ hybridization (FISH) pharmDxTM Assay Kit, Dako (2010) and PathVysion HER-2 DNA Probe Kit (Abbott Molecular) (2013)

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Summary

Introduction

In developed countries the second cause of mortality is that of the cancer, just after the cardiovascular diseases as noted in World Health Organization (WHO) reports ( 2014). Very often (in 20% to 25% cases), this cancer is followed by the over-expression of the glycoprotein HER2 (human epidermal growth factor receptor 2, called HER2/neu, or c-erb-B2) (Akiyama et al 1986) which is located on the surface of breast cells and is responsible for the cell growth, differentiation and division. The HER2 receptor is controlled by HER2 gene located at the cell’s nucleus, at chromosome 17 near to its centromere (CEP-17). In some cases HER2 gene is amplified, having more than two copies. This leads to increased synthesis of HER2 protein protein level may be even 100 times or more of those in

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Problem statement and related work
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Fractals and multifractals
Multifractal-based cell nuclei segmentation
Experimental system
Testing results and discussion
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Step Procedure
Conclusion
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Findings
Compliance with ethical standards
Full Text
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