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

cyclinD1 和 Ki67 联合应用对管腔型乳腺癌患者预后评估

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作者:Junmei Hao, Wenfeng Zhang, Yan Lyu, Jiarui Zou, Yunyun Zhang, Jiahong Lyu, Jianbo Zhang, Shuishan Xie, Cuiping Zhang, Jiandi Zhang, Fangrong Tang

Background

Ki67 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.

Conclusion

The current study supports the prospective investigation of cyclinD1 relevance in the clinic.

Methods

Both 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.

Results

cyclinD1 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.

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