Quantitative diagnosis of HER2 protein expressing breast cancer by single‐particle quantum dot imaging

摘要

Overexpression of HER2 is one of the major causes of breast cancer, and therefore precise diagnosis of its protein expression level is important. However, current methods estimating the HER2‐expression level are insufficient due to problem with the lack of quantification. This might result in a gap between diagnostics and therapeutics targeting HER2. Therefore, a new effective diagnostic method is needed. We developed a new immunohistochemical (IHC) technique with quantum dots (QD)‐conjugated trastuzumab using single‐particle imaging to quantitatively measure the HER2 expression level. Tissues from 37 breast cancer patients with available detailed clinical information were tested by IHC with QDs (IHC‐QD) and the correlation with IHC with 3,3′‐diaminobenzidine (DAB), fluorescence in situ hybridization (FISH), and IHC‐QD was examined. The number of QD‐conjugated trastuzumab particles binding specifically to a cancer cell was precisely calculated as the style="fixed-case">IHC‐ style="fixed-case">QD score. The style="fixed-case">IHC‐ style="fixed-case">QD score in 37 cases was correlated proportionally with the score of style="fixed-case">HER2 gene copy number as assessed by style="fixed-case">FISH (R = 0.83). When style="fixed-case">HER2 positivity was judged to be positive, the style="fixed-case">IHC‐ style="fixed-case">QD score with our cut‐off level was exactly concordant with the style="fixed-case">FISH score with a cut‐off value of 2.0. Furthermore, style="fixed-case">IHC‐ style="fixed-case">QDs score and time to progression ( style="fixed-case">TTP) of trastuzumab therapy were well correlated in style="fixed-case">HER2‐positive cases (R = 0.69). Conversely, the correlation between style="fixed-case">FISH score and style="fixed-case">TTP was not observed. We developed a precisely quantitative style="fixed-case">IHC method using trastuzumab‐conjugated style="fixed-case">QDs and single‐particle imaging analysis and propose the possibility of using style="fixed-case">IHC‐ style="fixed-case">QDs score as a predictive factor for trastuzumab therapy.