Abstract

Currently, there are no recommended alternative assays for HER2 cases deemed equivocal by immunohistochemistry and fluorescent in situ hybridization. Digital PCR (ddPCR), a highly accurate method to determine DNA copy number, could be a robust alternative for clinical HER2 diagnostics. HER2 and CEP17 copy numbers were quantified using two ddPCR platforms (QX200 and RainDrop) in 102 samples of invasive breast cancers. Compared to routine assays, ddPCR gave a sensitivity and specificity of 82.8% and 97.3% respectively, with a kappa value of 0.833 (p < 0.001). Moreover, the method proved to be robust as the results from two platforms was highly correlated (R2 = 0.91; Concordance rate = 97%; κ = 0.923, P < 0.001). Its performance was further tested on 114 HER2 equivocal cases in an independent validation cohort. 75% (21/28) of cases with HER2 amplification and 95% (82/86) of HER2 non-amplified case were classified as positive and negative by ddPCR respectively (κ = 0.709, P < 0.001). Notably, in the HER2 amplified cases, a lower percentage of HER2 positive cells could be related to the discordant results. Altogether, ddPCR is a robust alternative for clinical HER2 diagnostics. However, intratumoral heterogeneity of HER2 status still pose a challenge for HER2 analysis by ddPCR.

Details

Title
Robust and accurate digital measurement for HER2 amplification in HER2 equivocal breast cancer diagnosis
Author
Wang, Yuefeng 1 ; Tsang, Julia Y S 2 ; Cui, Yongmei 1 ; Cui, Ji 3 ; Lin, Ying 4 ; Zhao, Songli 5 ; Law, Patrick T W 6 ; Sai Yin Cheung 7 ; Ng, Enders K O 6 ; Tse, Gary M K 2 ; Zunfu Ke 1 

 Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 
 Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China 
 Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 
 Breast Disease Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China 
 Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Department of Pathology, Sanshui General Hospital, Foshan, China 
 Pangenia Lifesciences Limited, Hong Kong, China 
 Department of Pathology, Tuen Mun Hospital, Hong Kong, China 
Pages
1-8
Publication year
2017
Publication date
Jul 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1957849269
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.