TY - JOUR
T1 - Chromogenic in situ hybridisation for the assessment of HER2 status in breast cancer: an international validation ring study
AU - van de Vijver, Marc J.
AU - Bilous, Michael
AU - Hanna, Wedad
AU - Hofmann, Manfred
AU - Kristel, Petra
AU - Penault-Llorca, Frederique
AU - Ruschoff, Josef
PY - 2007
Y1 - 2007
N2 - ABSTRACT: INTRODUCTION: Before any new methodology can be introduced into the routine diagnostic setting it must be technically validated against the established standards. To this end, a ring study involving five international pathology laboratories was initiated to validate chromogenic in situ hybridisation (CISHTM) against fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) as a test for assessing human epidermal growth factor receptor-2 (HER2) status in breast cancer. METHODS: Each laboratory performed CISHTM, FISH and IHC on its own samples. Unstained sections from each case were also sent to another participating laboratory for blinded retesting by CISHTM ('outside CISHTM'). RESULTS: A total of 211 invasive breast carcinoma cases were tested. In 76 cases with high amplification (HER2/CEP17 ratio >4.0) by FISH, 73 cases (96%) scored positive (scores [greater than or equal to] 6) by 'outside CISHTM'. For FISH-negative cases (HER2/CEP17 ratio <2.0), 94 of 100 cases (94%) had CISHTM scores indicating no amplification (score GBP5), and only three cases were positive by CISHTM; in the three remaining cases, no CISHTM result could be obtained. For cases with low-level amplification using FISH (HER2/CEP17 ratio 2.0-4.0), 20 of 35 had CISHTM scores indicating gene amplification. Inter-laboratory concordance for was also very high: 95% for normal HER2 copy number (1-5 copies); and 92% for cases with HER2 copy numbers [greater than or equal to] 6. CISHTM intra-laboratory concordance with IHC was 92% for IHC-negative cases (IHC 0/1+) and 91% for IHC 3+ cases. Among IHC 2+ cases, CISHTM was 100% concordant with samples showing high amplification by FISH, and 94% concordant with FISH-negative samples. CONCLUSION: These results show that CISHTM inter-and intra-laboratory concordance to FISH and IHC is very high, even in equivocal IHC 2+ cases. Therefore, we conclude that CISHTM is a methodology that is a viable alternative to FISH in the HER2 testing algorithm
AB - ABSTRACT: INTRODUCTION: Before any new methodology can be introduced into the routine diagnostic setting it must be technically validated against the established standards. To this end, a ring study involving five international pathology laboratories was initiated to validate chromogenic in situ hybridisation (CISHTM) against fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) as a test for assessing human epidermal growth factor receptor-2 (HER2) status in breast cancer. METHODS: Each laboratory performed CISHTM, FISH and IHC on its own samples. Unstained sections from each case were also sent to another participating laboratory for blinded retesting by CISHTM ('outside CISHTM'). RESULTS: A total of 211 invasive breast carcinoma cases were tested. In 76 cases with high amplification (HER2/CEP17 ratio >4.0) by FISH, 73 cases (96%) scored positive (scores [greater than or equal to] 6) by 'outside CISHTM'. For FISH-negative cases (HER2/CEP17 ratio <2.0), 94 of 100 cases (94%) had CISHTM scores indicating no amplification (score GBP5), and only three cases were positive by CISHTM; in the three remaining cases, no CISHTM result could be obtained. For cases with low-level amplification using FISH (HER2/CEP17 ratio 2.0-4.0), 20 of 35 had CISHTM scores indicating gene amplification. Inter-laboratory concordance for was also very high: 95% for normal HER2 copy number (1-5 copies); and 92% for cases with HER2 copy numbers [greater than or equal to] 6. CISHTM intra-laboratory concordance with IHC was 92% for IHC-negative cases (IHC 0/1+) and 91% for IHC 3+ cases. Among IHC 2+ cases, CISHTM was 100% concordant with samples showing high amplification by FISH, and 94% concordant with FISH-negative samples. CONCLUSION: These results show that CISHTM inter-and intra-laboratory concordance to FISH and IHC is very high, even in equivocal IHC 2+ cases. Therefore, we conclude that CISHTM is a methodology that is a viable alternative to FISH in the HER2 testing algorithm
U2 - https://doi.org/10.1186/bcr1776
DO - https://doi.org/10.1186/bcr1776
M3 - Article
C2 - 17922920
SN - 1465-5411
VL - 9
SP - R68
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 5
ER -