Combined Use of cyclinD1 and Ki67 for Prognosis of Luminal-Like Breast Cancer Patients

BackgroundKi67 is a biomarker of proliferation to be used in immunohistochemistry (IHC)-based surrogate assay to determine the necessity of cytotoxic therapy for Luminal-like breast cancer patients. cyclinD1 is another frequently used biomarker of proliferation. A retrospective study was performed h...

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Main Authors: Junmei Hao, Wenfeng Zhang, Yan Lyu, Jiarui Zou, Yunyun Zhang, Jiahong Lyu, Jianbo Zhang, Shuishan Xie, Cuiping Zhang, Jiandi Zhang, Fangrong Tang
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-11-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.737794/full
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author Junmei Hao
Wenfeng Zhang
Yan Lyu
Jiarui Zou
Yunyun Zhang
Jiahong Lyu
Jianbo Zhang
Shuishan Xie
Cuiping Zhang
Jiandi Zhang
Fangrong Tang
author_facet Junmei Hao
Wenfeng Zhang
Yan Lyu
Jiarui Zou
Yunyun Zhang
Jiahong Lyu
Jianbo Zhang
Shuishan Xie
Cuiping Zhang
Jiandi Zhang
Fangrong Tang
author_sort Junmei Hao
collection DOAJ
description BackgroundKi67 is a biomarker of proliferation to be used in immunohistochemistry (IHC)-based surrogate assay to determine the necessity of cytotoxic therapy for Luminal-like breast cancer patients. cyclinD1 is another frequently used biomarker of proliferation. A retrospective study was performed here to investigate if these two biomarkers may be combined to improve the prognosis of Luminal-like patients.MethodsBoth Ki67 and cyclinD1 protein levels were measured absolutely and quantitatively using Quantitative Dot Blot method in 143 Luminal-like specimens. Optimized cutoffs for these two biomarkers were developed to evaluate their prognostic roles using Kaplan–Meier overall survival (OS) analysis.ResultscyclinD1 was found as an independent prognostic factor from Ki67 in univariate and multivariate OS analyses. At optimized cutoffs (cyclinD1 at 0.44 μmol/g and Ki67 at 2.31 nmol/g), the subgroup with both biomarkers below the cutoffs (n = 65) had 10-year survival probability at 90% in comparison to those with both biomarkers above the cutoffs (n = 18) with 8-year survival probability at 26% (log-rank test, p <0.0001). This finding was used to modify the surrogate assay using IHC-based cyclinD1 scores, with p-value decreased from 0.031 to 0.00061 or from 0.1 to 0.02, when the Ki67 score of 14 or 20% was used as cutoff, respectively, in the surrogate assay.ConclusionThe current study supports the prospective investigation of cyclinD1 relevance in the clinic.
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spelling doaj.art-7d3287aa92df48ea9ea56251068666fa2022-12-21T19:53:51ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-11-011110.3389/fonc.2021.737794737794Combined Use of cyclinD1 and Ki67 for Prognosis of Luminal-Like Breast Cancer PatientsJunmei Hao0Wenfeng Zhang1Yan Lyu2Jiarui Zou3Yunyun Zhang4Jiahong Lyu5Jianbo Zhang6Shuishan Xie7Cuiping Zhang8Jiandi Zhang9Fangrong Tang10Department of Pathology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, ChinaYantai Quanticision Diagnostics, Inc., Yantai, ChinaYantai Quanticision Diagnostics, Inc., Yantai, ChinaDepartment of Pathology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, ChinaYantai Quanticision Diagnostics, Inc., Yantai, ChinaYantai Quanticision Diagnostics, Inc., Yantai, ChinaYantai Quanticision Diagnostics, Inc., Yantai, ChinaDepartment of Pathology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, ChinaDepartment of Pathology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, ChinaYantai Quanticision Diagnostics, Inc., Yantai, ChinaYantai Quanticision Diagnostics, Inc., Yantai, ChinaBackgroundKi67 is a biomarker of proliferation to be used in immunohistochemistry (IHC)-based surrogate assay to determine the necessity of cytotoxic therapy for Luminal-like breast cancer patients. cyclinD1 is another frequently used biomarker of proliferation. A retrospective study was performed here to investigate if these two biomarkers may be combined to improve the prognosis of Luminal-like patients.MethodsBoth Ki67 and cyclinD1 protein levels were measured absolutely and quantitatively using Quantitative Dot Blot method in 143 Luminal-like specimens. Optimized cutoffs for these two biomarkers were developed to evaluate their prognostic roles using Kaplan–Meier overall survival (OS) analysis.ResultscyclinD1 was found as an independent prognostic factor from Ki67 in univariate and multivariate OS analyses. At optimized cutoffs (cyclinD1 at 0.44 μmol/g and Ki67 at 2.31 nmol/g), the subgroup with both biomarkers below the cutoffs (n = 65) had 10-year survival probability at 90% in comparison to those with both biomarkers above the cutoffs (n = 18) with 8-year survival probability at 26% (log-rank test, p <0.0001). This finding was used to modify the surrogate assay using IHC-based cyclinD1 scores, with p-value decreased from 0.031 to 0.00061 or from 0.1 to 0.02, when the Ki67 score of 14 or 20% was used as cutoff, respectively, in the surrogate assay.ConclusionThe current study supports the prospective investigation of cyclinD1 relevance in the clinic.https://www.frontiersin.org/articles/10.3389/fonc.2021.737794/fullQDBFFPEKi67Luminal-likebreast cancercyclin D1
spellingShingle Junmei Hao
Wenfeng Zhang
Yan Lyu
Jiarui Zou
Yunyun Zhang
Jiahong Lyu
Jianbo Zhang
Shuishan Xie
Cuiping Zhang
Jiandi Zhang
Fangrong Tang
Combined Use of cyclinD1 and Ki67 for Prognosis of Luminal-Like Breast Cancer Patients
Frontiers in Oncology
QDB
FFPE
Ki67
Luminal-like
breast cancer
cyclin D1
title Combined Use of cyclinD1 and Ki67 for Prognosis of Luminal-Like Breast Cancer Patients
title_full Combined Use of cyclinD1 and Ki67 for Prognosis of Luminal-Like Breast Cancer Patients
title_fullStr Combined Use of cyclinD1 and Ki67 for Prognosis of Luminal-Like Breast Cancer Patients
title_full_unstemmed Combined Use of cyclinD1 and Ki67 for Prognosis of Luminal-Like Breast Cancer Patients
title_short Combined Use of cyclinD1 and Ki67 for Prognosis of Luminal-Like Breast Cancer Patients
title_sort combined use of cyclind1 and ki67 for prognosis of luminal like breast cancer patients
topic QDB
FFPE
Ki67
Luminal-like
breast cancer
cyclin D1
url https://www.frontiersin.org/articles/10.3389/fonc.2021.737794/full
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