Abstract
Background and objectives: The currently used immunohistochemical approach in determining the estrogen receptor (ER) positivity of breast cancers (BCs) is inherently subjective and additionally limited by its semi-quantitative nature. The application of software in the analysis of digitized slide images may overcome some of these limitations. However, the utilization of such an approach requires that the entire staining procedure is standardized. Background and objectives: We aimed to establish a procedure for the photometric and morphometric analysis of BC immunohistochemical parameters that can possibly be used for a diagnostic purpose that is in line with the current semi-quantitative scoring system. Materials and Methods: Semi-quantitative analysis of ER-stained tissue sections was performed following the Allred scoring system guidelines. The quantitative analysis was performed in ImageJ software after color deconvolution. The quantitative analysis of 66 cases of invasive lobular BC included: Percent of ER-positive cells, average nuclear coloration intensity, and the quantitative ER score. The percent of ER-positive tumor cells was counted using a standard grid overlay, while optical density (0.0–1.0) was measured within each nucleus at the grid points. Results: A statistical analysis revealed a significant positive correlation (r = 0.886, p < 0.001) between the subjective semi-quantitative and quantitative ER scores, with a large effect size (d = 3.8215). We observed strong statistically significant correlations between individual parameters of the total ER score, percentage of ER-positive nuclei, and color intensity, obtained by the two independent methods. Conclusions: Additionally, besides excluding subjectivity, the up to now unreported cases of 3 + 0, 4 + 0, and 5 + 0 Allred scores were detected only by the application of the proposed quantitative approach.
Highlights
Around 70% of human breast cancers (BCs) express estrogen receptors (ERs) and, based on many demands, BCs are divided into estrogen-dependent and independent ones [1].Estrogen, as a transcription factor, regulates the genetically-programmed progression of cell cycle and growth in mammary glands
Having in mind that the ER-positivity score and patient survival correlate positively [17], and the need for an objective ER quantification, we aimed to establish a procedure for the photometric and morphometric analysis of BC immunohistochemical parameters corresponding to BCs with different biological aggressiveness, that can possibly be used for differential diagnostic purposes that are in line with the current semi-quantitative scoring system
Out of all cases diagnosed with BC during a two-year period (2009–2011), 66 cases of invasive lobular carcinomas (ILCs) belonging to the two most common variants were chosen for this analysis
Summary
Around 70% of human breast cancers (BCs) express estrogen receptors (ERs) and, based on many demands (diagnosis, therapy, etc.), BCs are divided into estrogen-dependent and independent ones [1].Estrogen, as a transcription factor, regulates the genetically-programmed progression of cell cycle and growth in mammary glands. The cases when one should suspect false ER (−) BCs might include tubular, lobular, and mucous histological types with a Nottingham score of 1, i.e., the current tumor is ER (−), the tumors with the same nuclear grade or Nottingham score are most often ER (+). Based on the correlation analysis of “cut-point” immunohistochemical scores and patient survival, it was concluded that patients with. The currently used immunohistochemical approach in determining the estrogen receptor (ER) positivity of breast cancers (BCs) is inherently subjective and limited by its semi-quantitative nature. Background and objectives: We aimed to establish a procedure for the photometric and morphometric analysis of BC immunohistochemical parameters that can possibly be used for a diagnostic purpose that is in line with the current semi-quantitative scoring system. Materials and Methods: Semi-quantitative analysis of ER-stained tissue sections was performed following the Allred scoring system guidelines.
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