title: Predictive diagnosis of the risk of breast cancer recurrence after surgery by single-particle quantum dot imaging.
abstract: In breast cancer, the prognosis of human epidermal growth factor receptor 2 (HER2)-positive patients (20-25%) has been dramatically improved by the clinical application of the anti-HER2 antibody drugs trastuzumab and pertuzumab. However, the clinical outcomes of HER2-negative cases with a poor prognosis have not improved, and novel therapeutic antibody drugs or diagnostic molecular markers of prognosis are urgently needed. Here, we targeted protease-activated receptor 1 (PAR1) as a new biomarker for HER2-negative patients. The developed anti-PAR1 antibody inhibited PAR1 activation by matrix metalloprotease 1 and thereby prevented cancer-cell migration and invasion. To estimate PAR1 expression levels in HER2-negative patient tissues using the antibody, user-friendly immunohistochemistry with fluorescence nanoparticles or quantum dots (QDs) was developed. Previously, immunohistochemistry with QDs was affected by tissue autofluorescence, making quantitative measurement extremely difficult. We significantly improved the quantitative sensitivity of immunohistochemistry with QDs by using an autofluorescence-subtracted image and single-QD imaging. The immunohistochemistry showed that PAR1 expression was strongly correlated with relapse-free survival time in HER2-negative breast cancer patients. Therefore, the developed anti-PAR1 antibody is a strong candidate for use as an anticancer drug and a prognostic biomarker for HER2-negative patients.
authors.affiliation: Department of Medical Physics, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.|Department of Nano-Medical Science, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Gonda
authors.affiliation: Department of Surgical Oncology, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Miyashita
authors.affiliation: Department of Physics, Graduate School of Science, University of Tokyo, Hongo Bunkyou-ku Tokyo 113-0033, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Higuchi
authors.affiliation: Department of Surgical Oncology, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tada
authors.affiliation: Laboratory for Comprehensive Bioimaging, RIKEN Quantitative Biology Center, 6-2-3, Furuedai, Suita, Osaka 565-0874, Japan.
authors.forename: Tomonobu M
authors.initials: TM
authors.lastname: Watanabe
authors.affiliation: Department of Pathology, Tohoku University Hospital, Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Surgical Oncology, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Department of Nano-Medical Science, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.|Department of Surgical Oncology, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Ohuchi
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D009367:Neoplasm Staging; D011182:Postoperative Care; D011379:Prognosis; D045663:Quantum Dots; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D044463:Receptor, PAR-1 / Q000276:immunology; D010975:Platelet Aggregation Inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D020781:Matrix Metalloproteinase 1; D018719:Erb-b2 Receptor Tyrosine Kinases; D044463:Receptor, PAR-1; D010975:Platelet Aggregation Inhibitors