Color Standardization and Stain Intensity Calibration for Whole Slide Image-Based Immunohistochemistry Assessment.

Automated quantification of human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) using whole slide imaging (WSI) is expected to eliminate subjectivity in visual assessment. However, the color intensity in WSI varies depending on the staining process and scanner device. Such variations affect the image analysis results. This paper presents methods to diminish the influence of color variation produced in the staining process using a calibrator slide consisting of peptide-coated microbeads. The calibrator slide is stained along with tissue sample slides, and the 3,3'-diaminobenzidine (DAB) color intensities of the microbeads are used for calibrating the color variation of the sample slides. An off-the-shelf image analysis tool is employed for the automated assessment, in which cells are classified by the thresholds for the membrane staining. We have adopted two methods for calibrating the color variation based on the DAB color intensities obtained from the calibrator slide: (1) thresholds for classifying the DAB membranous intensity are adjusted, and (2) the color intensity of WSI is corrected. In the experiment, the calibrator slides and tissue of breast cancer slides were stained together on different days and used to test our protocol. With the proposed protocol, the discordance in the HER2 evaluation was reduced to one slide out of 120 slides.

Standardizing HER2 immunohistochemistry assessment: calibration of color and intensity variation in whole slide imaging caused by staining and scanning.

In the evaluation of human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) - one of the standard biomarkers for breast cancer- visual assessment is laborious and subjective. Image analysis using whole slide image (WSI) could produce more consistent results; however, color variability in WSIs due to the choice of stain and scanning processes may impact image analysis. We therefore developed a calibration protocol to diminish the staining and scanning variations of WSI using two calibrator slides. The IHC calibrator slide (IHC-CS) contains peptide-coated microbeads with different concentrations. The color distribution obtained from the WSI of stained IHC-CS reflects the staining process and scanner characteristics. A color chart slide (CCS) is also useful for calibrating the color variation due to the scanner. The results of the automated HER2 assessment were compared to confirm the effectiveness of two calibration slides. The IHC-CS and HER2 breast cancer cases were stained on different days. All stained slides and CCS were digitized by two different WSI scanners. Results revealed 100% concordance between automated evaluation and the pathologist's assessment with both the scanner and staining calibration. The proposed method may enable consistent evaluation of HER2.

[Chemotherapy for elderly colorectal cancer patients in a regional hospital--problems in regional cancer care].

At Nara Social Insurance Hospital, from January 2005 to September 2008, chemotherapy for older adult (>or=70) colorectal cancer patients was performed in 18 adjuvant cases and 10 advanced cases. In adjuvant cases, 18 out of 33 patients of >or= stage IIIa received chemotherapy, and 13 completed treatment safely. In advanced cases, all patients received FLOFOX or FOLFIRI, with or without bevacizumab as first-line treatment with a response rate of 50%. Although adverse events were relatively frequent in the older adult patients, there was no difference in the survival rate between elderly and younger patient groups. Cancer chemotherapy for older adults with a high comorbidity rate requires more skill and experience than for younger patients. It was possible even for a small-volume hospital, which plays an important role in regional medical service for elderly patients, to build up a system providing standard chemotherapy for colorectal cancer. However, considering the limited financial and human resources, it is essential to form a regional alliance of designated cancer care hospitals and other clinics in order to maintain the level of practice.