Free digital image analysis software helps to resolve equivocal scores in HER2 immunohistochemistry

Helin, H; Tuominen, Vilppu J.; Ylinen, Onni; Helin, Heikki; Isola, Jorma

doi:10.1007/s00428-015-1868-7

Cited by 45 publications

(42 citation statements)

References 40 publications

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“…Currently, the software-based automated morphometric analysis in pathology is applied in assessing IHC scores, measuring morphological parameters of microvessels and extracting cell nuclear features [37][38][39][40]. These practices assist pathological diagnoses and may exhibit prognostic and predictive values.…”

Section: Discussionmentioning

confidence: 99%

Microvascular fractal dimension predicts prognosis and response to chemotherapy in glioblastoma: an automatic image analysis study

Chen

Shi

et al. 2018

Laboratory Investigation

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The microvascular profile has been included in the WHO glioma grading criteria. Nevertheless, microvessels in gliomas of the same WHO grade, e.g., WHO IV glioblastoma (GBM), exhibit heterogeneous and polymorphic morphology, whose possible clinical significance remains to be determined. In this study, we employed a fractal geometry-derived parameter, microvascular fractal dimension (mvFD), to quantify microvessel complexity and developed a home-made macro in Image J software to automatically determine mvFD from the microvessel-stained immunohistochemical images of GBM. We found that mvFD effectively quantified the morphological complexity of GBM microvasculature. Furthermore, high mvFD favored the survival of GBM patients as an independent prognostic indicator and predicted a better response to chemotherapy of GBM patients. When investigating the underlying relations between mvFD and tumor growth by deploying Ki67/mvFD as an index for microvasculature-normalized tumor proliferation, we discovered an inverse correlation between mvFD and Ki67/mvFD. Furthermore, mvFD inversely correlated with the expressions of a glycolytic marker, LDHA, which indicated poor prognosis of GBM patients. Conclusively, we developed an automatic approach for mvFD measurement, and demonstrated that mvFD could predict the prognosis and response to chemotherapy of GBM patients.

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Section: Discussionmentioning

confidence: 99%

Microvascular fractal dimension predicts prognosis and response to chemotherapy in glioblastoma: an automatic image analysis study

Chen

Shi

et al. 2018

Laboratory Investigation

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“…Digital image analysis (DIA) has emerged as an alternative method to classify HER2 IHC. In breast cancer, a variety of DIA tools in different platforms is able to determine HER2 status accurately . DIA provides an objective and reproducible HER2 classification method to support pathologists in daily practice.…”

Section: Introductionmentioning

confidence: 99%

Digital image analysis of HER2 immunohistochemistry in gastric‐ and oesophageal adenocarcinoma: a validation study on biopsies and surgical specimens

et al. 2017

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Aims: To test the validity of diagnostics incorporating digital image analysis (DIA) for human epidermal growth factor 2 (HER2) immunohistochemistry (IHC) in gastro-oesophageal adenocarcinomas, as an alternative to current standard diagnostics using manual scoring. Methods and results: We included 319 consecutive gastro-oesophageal adenocarcinomas (232 biopsies and 87 surgical specimens). DIA was applied to determine HER2 IHC classification, using both standard breast cancer (BC) and modified gastro-oesophageal cancer (GEC) cut-offs. Consensus manual scores were established by four independent observers. Chromogenic in-situ hybridization (CISH) was performed on all 2+ cases by manual scoring, DIA or both. HER2 status was considered positive in 3+ and CISHpositive 2+ cases. Overall agreement between DIA and consensus manual scores was 76.5% (weighted j = 0.66, BC cut-offs) and 85.6% (weighted j = 0.80, GEC cut-offs). Agreement was similar for biopsies and surgical specimens. All disagreement occurred in the manual IHC equivocal cases. DIA resulted in a reduction of 2+ cases: 75.8% with BC cut-offs and 46.5% with GEC cut-offs. HER2 status was positive in 48 cases (15%) with standard diagnostics and DIA using GEC cut-offs, and 46 cases (14.4%) using BC cut-offs (all with CISH in 2+ cases). Considering standard diagnostics as a reference, DIA showed 93.8% sensitivity and 99.6% specificity (BC cut-offs) or 97.9% sensitivity and 99.6% specificity (GEC cut-offs). Conclusions: DIA is a reliable and feasible alternative to manual HER2 IHC scoring in gastro-oesophageal adenocarcinoma, both in biopsies and surgical specimens, leading to a reduction of 2+ cases for which subsequent ISH testing is required.

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“…Different approaches have been investigated for HER2-IHC image-analysis by using color intensities [ 28 , 29 ] or geometric properties of the staining pattern [ 30 ]. Recent advances in digital image analysis have shown to increase of inter-observer agreement and decrease of the number of equivocally scored cases [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Physical basis of the ‘magnification rule’ for standardized Immunohistochemical scoring of HER2 in breast and gastric cancer

et al. 2018

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BackgroundDetection of HER2/neu receptor overexpression and/or amplification is a prerequisite for efficient anti-HER2 treatment of breast and gastric carcinomas. Immunohistochemistry (IHC) of the HER2 protein is the most common screening test, thus precise and reproducible IHC-scoring is of utmost importance. Interobserver variance still is a problem; in particular in gastric carcinomas the reliable differentiation of IHC scores 2+ and 1+ is challenging.Herein we describe the physical basis of what we called the ‘magnification rule’: Different microscope objectives are employed to reproducibly subdivide the continuous spectrum of IHC staining intensities into distinct categories (1+, 2+, 3+).MethodsHER2-IHC was performed on 120 breast cancer biopsy specimens (n = 40 per category). Width and color-intensity of membranous DAB chromogen precipitates were measured by whole-slide scanning and digital morphometry. Image-analysis data were related to semi-quantitative manual scoring according to the magnification rule and to the optical properties of the employed microscope objectives.ResultsThe semi-quantitative manual HER2-IHC scores are correlated to color-intensity measured by image-analysis and to the width of DAB-precipitates. The mean widths ±standard deviations of precipitates were: IHC-score 1+, 0.64 ± 0.1 μm; score 2+, 1.0 ± 0.23 μm; score 3+, 2.14 ± 0.4 μm. The width of precipitates per category matched the optical resolution of the employed microscope objective lenses: Approximately 0.4 μm (40×), 1.0 μm (10×) and 2.0 μm (5×).ConclusionsPerceived intensity, width of the DAB chromogen precipitate, and absolute color-intensity determined by image-analysis are linked. These interrelations form the physical basis of the ‘magnification rule’: 2+ precipitates are too narrow to be observed with 5× microscope objectives, 1+ precipitates are too narrow for 10× objectives. Thus, the rule uses the optical resolution windows of standard diagnostic microscope objectives to derive the width of the DAB-precipitates. The width is in turn correlated with color-intensity. Hereby, the more or less subjective estimation of IHC scores based only on the staining-intensity is replaced by a quasi-morphometric measurement. The principle seems universally applicable to immunohistochemical stainings of membrane-bound biomarkers that require an intensity-dependent scoring.Electronic supplementary materialThe online version of this article (10.1186/s13000-018-0696-x) contains supplementary material, which is available to authorized users.

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Free digital image analysis software helps to resolve equivocal scores in HER2 immunohistochemistry

Cited by 45 publications

References 40 publications

Microvascular fractal dimension predicts prognosis and response to chemotherapy in glioblastoma: an automatic image analysis study

Microvascular fractal dimension predicts prognosis and response to chemotherapy in glioblastoma: an automatic image analysis study

Digital image analysis of HER2 immunohistochemistry in gastric‐ and oesophageal adenocarcinoma: a validation study on biopsies and surgical specimens

Physical basis of the ‘magnification rule’ for standardized Immunohistochemical scoring of HER2 in breast and gastric cancer

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