Quantitative diagnosis of HER2 protein expressing breast cancer by single-particle quantum dot imaging.
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 IHC-QD score. The IHC-QD score in 37 cases was correlated proportionally with the score of HER2 gene copy number as assessed by FISH (R = 0.83). When HER2 positivity was judged to be positive, the IHC-QD score with our cut-off level was exactly concordant with the FISH score with a cut-off value of 2.0. Furthermore, IHC-QDs score and time to progression (TTP) of trastuzumab therapy were well correlated in HER2-positive cases (R = 0.69). Conversely, the correlation between FISH score and TTP was not observed. We developed a precisely quantitative IHC method using trastuzumab-conjugated QDs and single-particle imaging analysis and propose the possibility of using IHC-QDs score as a predictive factor for trastuzumab therapy.
Department of Surgical Oncology, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.|Department of Nano-Medical Science, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
Minoru
M
Miyashita
Department of Nano-Medical Science, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. gonda@med.tohoku.ac.jp.|Department of Medical Physics, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. gonda@med.tohoku.ac.jp.
Kohsuke
K
Gonda
Department of Surgical Oncology, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
Hiroshi
H
Tada
Department of Pathology, Tohoku University Hospital, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
Mika
M
Watanabe
Department of Nano-Medical Science, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.|Department of Medical Physics, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
Narufumi
N
Kitamura
Department of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
Takashi
T
Kamei
Department of Pathology, Tohoku University Hospital, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
Hironobu
H
Sasano
Department of Surgical Oncology, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
Takanori
T
Ishida
Department of Surgical Oncology, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.|Department of Nano-Medical Science, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
Noriaki
N
Ohuchi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008875:Middle Aged; D011485:Protein Binding; D045663:Quantum Dots; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012680:Sensitivity and Specificity; D000072760:Single Molecule Imaging / Q000379:methods*; D000068878:Trastuzumab / Q000494:pharmacology*
D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
Breast cancer; HER2; quantum dot; single-particle imaging; trastuzumab
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