Image analysis as an adjunct to manual HER‐2 immunohistochemical review: a diagnostic tool to standardize interpretation

Abstract

Dobson L, Conway C, Hanley A, Johnson A, Costello S, O’Grady A, Connolly Y, Magee H, O’Shea D, Jeffers M & Kay E (2010) Histopathology57, 27–38 Image analysis as an adjunct to manual HER-2 immunohistochemical review: a diagnostic tool to standardize interpretationAims:Accurate determination of HER-2 status is critical to identify patients for whom trastuzumab treatment will be of benefit. Although the recommended primary method of evaluation is immunohistochemistry, numerous reports of variability in interpretation have raised uncertainty about the reliability of results. Recent guidelines have suggested that image analysis could be an effective tool for achieving consistent interpretation, and this study aimed to assess whether this technology has potential as a diagnostic support tool.Methods and results:Across a cohort of 275 cases, image analysis could accurately classify HER-2 status, with 91% agreement between computer-aided classification and the pathology review. Assessment of the continuity of membranous immunoreactivity in addition to intensity of reactivity was critical to distinguish between negative and equivocal cases and enabled image analysis to report a lower referral rate of cases for confirmatory fluorescence in situ hybridization (FISH) testing. An excellent concordance rate of 95% was observed between FISH and the automated review across 136 informative cases.Conclusions:This study has validated that image analysis can robustly and accurately evaluate HER-2 status in immunohistochemically stained tissue. Based on these findings, image analysis has great potential as a diagnostic support tool for pathologists and biomedical scientists, and may significantly improve the standardization of HER-2 testing by providing a quantitative reference method for interpretation.

Accurate breast cancer diagnosis through real-time PCR her-2 gene quantification using immunohistochemically-identified biopsies

“…It has been mentioned that IHC 2+ result variability is principally caused by tissue quality, fixation time, type of antibody used and lack of standardization among users (3,12). In this sense, our experience indicates that IHC 2+ misevaluation depends on low Her-2 protein levels contained in samples analyzed, but principally on resolution capacity limitations of IHC methodology to quantify low target protein levels.…”

Evaluation of HER2/neu Status by Immunohistochemistry Using Computer-Based Image Analysis and Correlation With Gene Amplification by Fluorescence In Situ Hybridization Assay: A 10-Year Experience and Impact of Test Standardization on Concordance Rate

“…26 A recent large study 34 reported the rate of IHC 2þ at 24% by manual scoring and 14% were amplified by FISH, using the ratio of greater than 2.0. The rate of IHC 2þ by IA in one study 17 was 11.2% and FISH was positive in 26% of the cases. In our study, the FISHþ rate ranged from 1% to 14% (median, 5.3%), although a higher FISHþ rate was seen from 2008 onward; however, this was associated with higher numbers of IHC 2þ cases.…”

“…9 One of the suggestions was that image analysis (IA) could be an effective tool for objective interpretation, and that validation and calibration of IA instrumentation is essential before implementation in the laboratory. Studies [10][11][12][13][14][15][16][17][18][19] have shown IA to be more objective and reproducible with higher correlation with the fluorescence in situ hybridization (FISH) assay. However, most of these studies included small series of cases and were not reflective of routine clinical practice.…”

Digital image analysis of membrane connectivity is a robust measure of HER2 immunostains

“…Hence, distinction between complete and incomplete membrane staining and cytoplasmic staining may be difficult. This may be one explanation for the high variation in concordance rates (75-91%) [16]. Recently, an IA system has been developed to assess the continuity of membrane immunoreactivity in addition to intensity, showing a concordance rate of 95% with FISH [16].…”