Accuracy of HER2 status determination on breast core-needle biopsies (immunohistochemistry, FISH, CISH and SISH vs FISH)

Abstract

Preoperative breast cancer diagnosis on core biopsies has become a standard of care in many countries. Controversies exist concerning the accuracy of HER2 testing on biopsies as compared with surgical specimens, and few data exist concerning the use of emerging technologies such as bright-field in-situ hybridization in such a setting. A French multicenter, cross-sectional, histopathological study assessed the concordance of HER2 status determined by immunohistochemistry and silver (SISH) or chromogenic in-situ hybridization (CISH) on core-needle biopsies with HER2 status determined by fluorescence in-situ hybridization (FISH) on surgical specimens. The concordance between biopsy and operative results was also assessed for each method. We studied 260 breast tumors from 24 centers between April 2003 and August 2009. Excellent concordance (j: 0.92-0.97) was shown between immunohistochemistry and FISH with low discordance rates (2-4%), high specificity (97-98%) and sensitivity values (95-99%), with no significant difference according to the immunohistochemistry interpretation guidelines used. The correlation between SISH and CISH on biopsies and FISH on surgical samples was strong (j: 0.96 and 0.94, respectively), with no significant difference between false negative rates or sensitivity and specificity values (2 and 5%, 99 and 96%, 98 and 98%, respectively). Whatever the evaluation technique, excellent concordance between biopsies and surgical specimens was observed (j X0.97; discordance rates between 1 and 2%), with high sensitivity (98-99%) and specificity (98-100%). Based on these results, when FISH cannot be used, SISH and/or CISH could be proposed as an alternative method to determine HER2 status and to confirm any ambiguous immunohistochemistry results, either for preoperative percutaneous biopsies or for surgical specimens. They could also be used for quality controls and immunohistochemistry calibration.

Concomitant Detection of HER2 Protein and Gene Alterations by Immunohistochemistry (IHC) and Silver Enhanced In Situ Hybridization (SISH) Identifies HER2 Positive Breast Cancer with and without Gene Amplification

“…Concordance between IHC and ISH technologies in HER2 status assessment in breast cancer has been the subject of several previous studies [3], [6], [18], [19]. These studies confirmed a realistic concordance between IHC and SISH technology, especially in settings where ISH is applied as reflex testing in IHC score 2+ cases.…”

The prognostic role of HER2 expression in ductal breast carcinoma in situ (DCIS); a population-based cohort study

“…A previous publication including a subset of this study population, showed an overall concordance of 80 % between TMAs and whole sections for IHC assessment of ER, PR, and HER2, and notably the prognostic value of these markers was similar irrespective of assessment based on TMA or whole sections [36]. This study is predominantly based on SISH regarding HER2 status with an anticipated high accuracy compared to IHC [37]. Breast conserving surgery represents the surgical intervention predominantly used in our cohort.…”

Determination of HER2 Gene Amplification in Breast Cancer using Dual-color Silver Enhanced in situ Hybridization (dc-SISH) and Comparison with Fluorescence ISH (FISH)

“…Pre-analytic factors affect the test results less than immunohistochemistry. Nevertheless, the FISH technique is more expensive, it necessitates special equipment and educated personnel, its application process lasts longer, and a fluorescent microscope is required for the evaluation of the test (Francis et al, 2009;Papouchado et al, 2010;Ying et al, 2010;Arnould et al, 2012;Schiavon et al, 2012). The SISH method, which can be an alternative to the FISH technique, is comprised of a multimer technology, combined with enzyme metallography, which allows for the identification of the HER2 oncogene amplification with silver marking.…”