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Clinical relevance of Ki67 gene expression analysis using formalin-fixed paraffin-embedded breast cancer specimens

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Abstract

Background

Ki67 is a protein associated with cell cycle activity and shows a good correlation with the growth fraction, which has been proposed as a prognostic or predictive marker in breast cancer. In this study, we aimed to analyze the expression levels of Ki67 (MKI67) messenger RNA (mRNA) derived from formalin-fixed paraffin-embedded (FFPE) tissues for comparison with the immunohistochemical Ki67 labeling index, and investigate the correlation coefficients with clinical outcomes.

Methods

We analyzed the data of Ki67 mRNA from FFPE and matched fresh-frozen (FF) tissues based on a real-time quantitative reverse-transcription polymerase chain reaction (RT-qPCR) assay system in 203 cases of primary invasive breast cancer.

Results

The correlation between Ki67 mRNA expression of either FFPE or FF specimens and Ki67 labeling index was positive, as was the correlation between the FFPE and FF results (P < 0.0001). Ki67 mRNA expression of FFPE specimens was significantly associated with clinicopathological characteristics: tumor size, lymph node status, nuclear grade, hormone receptors, human epidermal growth factor receptor 2 (Her2) status, and tumor subtype. In prognostic results, Ki67 gene expression in the FFPE specimens revealed almost similar patterns of significance in Kaplan–Meier curves and univariate and multivariate relapse-free survival results as the Ki67 labeling index.

Conclusions

Gene expression analysis of Ki67 of FFPE specimens could be successfully performed using RT-qPCR, closely resembling the significant clinical characteristics of Ki67 labeling index. These results confirm that Ki67 gene expression of FFPE specimens has potential for evaluation of cell cycle activity of breast cancer specimens.

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Acknowledgments

We thank Y. Azakami and Y. Sonoda for excellent technical support, and A. Okabe for clinical data management.

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Authors and Affiliations

  1. Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo Kumamoto, Kumamoto, 860-8556, Japan

    Satoko Yamamoto, Mutsuko Ibusuki, Yutaka Yamamoto, Saori Fujiwara, Keiichi Murakami & Hirotaka Iwase

  2. Department of General Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China

    Peifen Fu

Authors
  1. Satoko Yamamoto
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  2. Mutsuko Ibusuki
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  3. Yutaka Yamamoto
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  4. Peifen Fu
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  5. Saori Fujiwara
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  6. Keiichi Murakami
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  7. Hirotaka Iwase
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Corresponding author

Correspondence to Hirotaka Iwase.

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Yamamoto, S., Ibusuki, M., Yamamoto, Y. et al. Clinical relevance of Ki67 gene expression analysis using formalin-fixed paraffin-embedded breast cancer specimens. Breast Cancer 20, 262–270 (2013). https://doi.org/10.1007/s12282-012-0332-7

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  • DOI: https://doi.org/10.1007/s12282-012-0332-7

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