Abstract
BackgroundFluorescence in situ hybridization (FISH) is very accurate method for measuring HER2 gene copies, as a sign of potential breast cancer. This method requires small tissue samples, and has a high sensitivity to detect abnormalities from a histological section. By using multiple colors, this method allows the detection of multiple targets simultaneously. The target parts in the cells become visible as colored dots. The HER-2 probes are visible as orange stained spots under a fluorescent microscope while probes for centromere 17 (CEP-17), the chromosome on which the gene HER-2/neu is located, are visible as green spots.MethodsThe conventional analysis involves the scoring of the ratio of HER-2/neu over CEP 17 dots within each cell nucleus and then averaging the scores for a number of 60 cells. A ratio of 2.0 of HER-2/neu to CEP 17 copy number denotes amplification. Several methods have been proposed for the detection and automated evaluation (dot counting) of FISH signals. In this paper the combined method based on the mathematical morphology (MM) and inverse multifractal (IMF) analysis is suggested. Similar method was applied recently in detection of microcalcifications in digital mammograms, and was very successful.ResultsThe combined MM using top-hat and bottom-hat filters, and the IMF method was applied to FISH images from Molecular Biology Lab, Department of Pathology, Wielkoposka Cancer Center, Poznan. Initial results indicate that this method can be applied to FISH images for the evaluation of HER2/neu status.ConclusionsMathematical morphology and multifractal approach are used for colored dot detection and counting in FISH images. Initial results derived on clinical cases are promising. Note that the overlapping of colored dots, particularly red/orange dots, needs additional improvements in post-processing.
Highlights
Fluorescence in situ hybridization (FISH) is very accurate method for measuring human epidermal growth factor receptor 2 (HER2) gene copies, as a sign of potential breast cancer
After more decade of research, a drug Herceptin was discovered and approved for use by the U.S Food and Drug Administration (FDA) in September 1998, which can be very successful in treatment of advanced breast cancer just for women whose breast cancer cells carry extra copies of a HER2
FISH images are evaluated by skilled pathologist and tested by proposed methods
Summary
Detecting relatively small bright dots within the digital image was under the investigation of our recent research targeted to the detection of microcalcifications in digital (or digitized) mammograms [15,16,17]. Normal human tissue is characterized by high degree of self-similarity[19], while the tissue anomalies may be considered as structural “defects”, i.e., as deviations from global regularity of the background This method is applied successfully for enhancing and detecting microcalcifications in digital mammograms [16]. Regarding to FISH images, colored dots can be assumed as parts characterized by high values of Hölder exponent a (high local changes) and low values of its distribution f(a) (rare events, in global sense). Under these assumption, by applying IMF we can extract colored dots from nuclei background
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