Development of an intraoperative breast cancer margin assessment method using quantitative fluorescence measurements

Abstract Breast-conserving surgery has become the preferred treatment method for breast cancer. Surgical margin assessment is performed during surgery, as it can reduce local recurrence in the preserved breast. Development of reliable and lower-cost ex vivo cancer detection methods would offer sever...

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Main Authors: Hiroki Ueo, Itsushi Minoura, Hiroaki Ueo, Ayako Gamachi, Yuichiro Kai, Yoko Kubota, Takako Doi, Miki Yamaguchi, Toshinari Yamashita, Hitoshi Tsuda, Takuya Moriya, Rin Yamaguchi, Yuji Kozuka, Takeshi Sasaki, Takaaki Masuda, Yasuteru Urano, Masaki Mori, Koshi Mimori
Format: Article
Language:English
Published: Nature Portfolio 2022-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-12614-6
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author Hiroki Ueo
Itsushi Minoura
Hiroaki Ueo
Ayako Gamachi
Yuichiro Kai
Yoko Kubota
Takako Doi
Miki Yamaguchi
Toshinari Yamashita
Hitoshi Tsuda
Takuya Moriya
Rin Yamaguchi
Yuji Kozuka
Takeshi Sasaki
Takaaki Masuda
Yasuteru Urano
Masaki Mori
Koshi Mimori
author_facet Hiroki Ueo
Itsushi Minoura
Hiroaki Ueo
Ayako Gamachi
Yuichiro Kai
Yoko Kubota
Takako Doi
Miki Yamaguchi
Toshinari Yamashita
Hitoshi Tsuda
Takuya Moriya
Rin Yamaguchi
Yuji Kozuka
Takeshi Sasaki
Takaaki Masuda
Yasuteru Urano
Masaki Mori
Koshi Mimori
author_sort Hiroki Ueo
collection DOAJ
description Abstract Breast-conserving surgery has become the preferred treatment method for breast cancer. Surgical margin assessment is performed during surgery, as it can reduce local recurrence in the preserved breast. Development of reliable and lower-cost ex vivo cancer detection methods would offer several benefits for patient care. Here, a practical and quantitative evaluation method for the ex vivo fluorescent diagnosis of breast lesions was developed and confirmed through a three-step clinical study. Gamma-glutamyl-hydroxymethyl rhodamine green (gGlu-HMRG) has been reported to generate fluorescence in breast lesions. Using this probe, we constructed a reliable and reproducible procedure for the quantitative evaluation of fluorescence levels. We evaluated the reliability of the method by considering reproducibility, temperature sensitivity, and the effects of other clinicopathological factors. The results suggest that the fluorescence increase of gGlu-HMRG is a good indicator of the malignancy of breast lesions. However, the distributions overlapped. A 5 min reaction with this probe could be used to distinguish at least part of the normal breast tissue. This method did not affect the final pathological examination. In summary, our results indicate that the methods developed in this study may serve as a feasible intraoperative negative-margin assessment tool during breast-conserving surgery.
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spelling doaj.art-57841e403e1d428fb43fed7ca65cece22022-12-22T00:23:22ZengNature PortfolioScientific Reports2045-23222022-05-0112111010.1038/s41598-022-12614-6Development of an intraoperative breast cancer margin assessment method using quantitative fluorescence measurementsHiroki Ueo0Itsushi Minoura1Hiroaki Ueo2Ayako Gamachi3Yuichiro Kai4Yoko Kubota5Takako Doi6Miki Yamaguchi7Toshinari Yamashita8Hitoshi Tsuda9Takuya Moriya10Rin Yamaguchi11Yuji Kozuka12Takeshi Sasaki13Takaaki Masuda14Yasuteru Urano15Masaki Mori16Koshi Mimori17Ueo Breast Cancer HospitalGoryo Chemical Inc.Ueo Breast Cancer HospitalDepartment of Pathology, Almeida Memorial HospitalUeo Breast Cancer HospitalUeo Breast Cancer HospitalBreast Cancer Center, Shonan Memorial HospitalDepartment of Breast Surgery, JCHO Kurume General HospitalDepartment of Breast and Endocrine Surgery, Kanagawa Cancer CenterDepartment of Basic Pathology, National Defense Medical CollegeDepartment of Pathology, Kawasaki Medical SchoolDepartment of Pathology and Laboratory Medicine, Kurume University Medical CenterDepartment of Pathology, Mie University HospitalDepartment of Next-Generation Pathology Information and Networking, Faculty of Medicine, The University of TokyoDepartment of Surgery, Kyushu University Beppu HospitalGraduate School of Medicine and Graduate School of Pharmaceutical Sciences, The University of TokyoDepartment of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Surgery, Kyushu University Beppu HospitalAbstract Breast-conserving surgery has become the preferred treatment method for breast cancer. Surgical margin assessment is performed during surgery, as it can reduce local recurrence in the preserved breast. Development of reliable and lower-cost ex vivo cancer detection methods would offer several benefits for patient care. Here, a practical and quantitative evaluation method for the ex vivo fluorescent diagnosis of breast lesions was developed and confirmed through a three-step clinical study. Gamma-glutamyl-hydroxymethyl rhodamine green (gGlu-HMRG) has been reported to generate fluorescence in breast lesions. Using this probe, we constructed a reliable and reproducible procedure for the quantitative evaluation of fluorescence levels. We evaluated the reliability of the method by considering reproducibility, temperature sensitivity, and the effects of other clinicopathological factors. The results suggest that the fluorescence increase of gGlu-HMRG is a good indicator of the malignancy of breast lesions. However, the distributions overlapped. A 5 min reaction with this probe could be used to distinguish at least part of the normal breast tissue. This method did not affect the final pathological examination. In summary, our results indicate that the methods developed in this study may serve as a feasible intraoperative negative-margin assessment tool during breast-conserving surgery.https://doi.org/10.1038/s41598-022-12614-6
spellingShingle Hiroki Ueo
Itsushi Minoura
Hiroaki Ueo
Ayako Gamachi
Yuichiro Kai
Yoko Kubota
Takako Doi
Miki Yamaguchi
Toshinari Yamashita
Hitoshi Tsuda
Takuya Moriya
Rin Yamaguchi
Yuji Kozuka
Takeshi Sasaki
Takaaki Masuda
Yasuteru Urano
Masaki Mori
Koshi Mimori
Development of an intraoperative breast cancer margin assessment method using quantitative fluorescence measurements
Scientific Reports
title Development of an intraoperative breast cancer margin assessment method using quantitative fluorescence measurements
title_full Development of an intraoperative breast cancer margin assessment method using quantitative fluorescence measurements
title_fullStr Development of an intraoperative breast cancer margin assessment method using quantitative fluorescence measurements
title_full_unstemmed Development of an intraoperative breast cancer margin assessment method using quantitative fluorescence measurements
title_short Development of an intraoperative breast cancer margin assessment method using quantitative fluorescence measurements
title_sort development of an intraoperative breast cancer margin assessment method using quantitative fluorescence measurements
url https://doi.org/10.1038/s41598-022-12614-6
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