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Overexpression of metadherin/MTDH is associated with an aggressive phenotype and a poor prognosis in invasive breast cancer

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Abstract

Background

Metadherin (MTDH) plays functional roles in the tumorigenesis and tumor progression of various cancers. This study investigated the associations between MTDH and the clinicopathological features in primary breast carcinomas to clarify the role of MTDH in the phenotypes and prognosis of breast cancer.

Methods

A total of 195 primary invasive breast cancer samples were evaluated. The MTDH DNA copy number and MTDH mRNA expression were analyzed by quantitative genomic polymerase chain reaction (PCR) and quantitative reverse transcriptase PCR. MTDH protein expression was analyzed by immunohistochemistry.

Results

A positive correlation was found between the expression of MTDH protein and mRNA expression and the MTDH DNA copy number. MTDH overexpression was significantly associated with a high nuclear grade, negative estrogen receptor (ER) and progesterone receptor (PR) expression, high Ki67 index, poor disease-free survival (P = 0.0001), poor distant metastasis-free survival (P = 0.009), and poor overall survival (P = 0.0101). MTDH overexpression showed a particularly negative impact on the prognosis in node-negative patients. A multivariate analysis showed MTDH overexpression to be independently associated with a poor disease-free survival rate [HR 3.45, 95 % confidence interval (CI) 1.69–6.84, P = 0.0010] and a poor distant metastasis-free survival rate (HR 2.39, 95 % CI 1.08–5.01, P = 0.0319).

Conclusion

MTDH overexpression contributes to an aggressive phenotype, thus leading to a poor prognosis for primary invasive breast cancer.

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Acknowledgments

This study was supported by grants from the Ministry of Education, Culture, Sports Science, and Technology of Japan. We are grateful to Ms. Takako Shishino, Ms. Megumi Kiyota, and Ms. Yuko Kubota for their valuable technical assistance. We are also grateful to Dr. Natsumi Yamashita for statistical analyses.

Conflict of interest

The authors have no conflict of interest to declare.

Author information

Authors and Affiliations

  1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Eriko Tokunaga, Yuichiro Nakashima, Nami Yamashita, Yuichi Hisamatsu, Satoko Okada, Sayuri Akiyoshi, Masaru Morita & Yoshihiko Maehara

  2. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Shinichi Aishima

  3. Department of Molecular Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Hiroyuki Kitao

Authors
  1. Eriko Tokunaga
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  2. Yuichiro Nakashima
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  3. Nami Yamashita
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  4. Yuichi Hisamatsu
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  7. Shinichi Aishima
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  8. Hiroyuki Kitao
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  9. Masaru Morita
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  10. Yoshihiko Maehara
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Correspondence to Eriko Tokunaga.

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Tokunaga, E., Nakashima, Y., Yamashita, N. et al. Overexpression of metadherin/MTDH is associated with an aggressive phenotype and a poor prognosis in invasive breast cancer. Breast Cancer 21, 341–349 (2014). https://doi.org/10.1007/s12282-012-0398-2

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  • DOI: https://doi.org/10.1007/s12282-012-0398-2

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