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In phyllodes tumors of the breast expression of SPARC (osteonectin/BM40) mRNA by in situ hybridization correlates with protein expression by immunohistochemistry and is associated with tumor progression

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Abstract

Secreted protein acidic and rich in cysteine (SPARC) plays an essential role in tumor invasion and metastasis. The present work was undertaken to detect expression of SPARC mRNA in phyllodes tumors (PTs) and its association with SPARC protein expression. This study also evaluated expression of SPARC mRNA and its correlation between grade and clinical behavior of PTs. In addition, we assessed in PTs the association of expression of SPARC with that of matrix metalloproteinase (MMP)-2 and of MMP-9. SPARC mRNA expression was determined by RNAscope in situ hybridization (ISH) in 50 benign, 22 borderline, and 10 malignant PTs using a tissue microarray. Furthermore, we applied immunohistochemistry (IHC) to examine expression of SPARC, MMP-2, and MMP-9. SPARC mRNA appeared to be concentrated mainly in the stromal compartment of PTs. IHC staining patterns of SPARC protein showed concordance with SPARC mRNA ISH results. Stromal SPARC expression increased continuously as PTs progress from benign through borderline to malignant PTs, both at mRNA (using ISH) (P = 0.044) and protein level (using IHC) (P = 0.000). The recurrence percentage was higher in the stromal SPARC mRNA or protein-positive group than in the SPARC-negative group but this difference was not statistically significant. Stromal SPARC mRNA and protein expression was associated with PT grade and correlated with MMP-2 expression. These results indicate that SPARC-mediated degradation of the extracellular matrix, and its possible association with MMPs, might contribute to progression of PTs.

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Acknowledgements

This manuscript was presented in part at the 10 European Breast Cancer Conference, Amsterdam, March 9–11, 2016.

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Authors and Affiliations

  1. Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea

    Nah Ihm Kim, Ga-Eon Kim & Ji Shin Lee

  2. Department of Pathology, Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-gun, Jeollanam-do, 519-809, Republic of Korea

    Ji Shin Lee

  3. Department of Surgery, Chonnam National University Medical School, Gwangju, Republic of Korea

    Min Ho Park

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  1. Nah Ihm Kim
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Corresponding author

Correspondence to Ji Shin Lee.

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This study was approved by the Institutional Review Board (IRB) at the Chonnam National University Hwasun Hospital (Jeollanam-do, Korea) (CNUHH-2014-155).

Funding

This study was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2011-0030034).

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The authors declare that they have no conflict of interest.

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Kim, N.I., Kim, GE., Lee, J.S. et al. In phyllodes tumors of the breast expression of SPARC (osteonectin/BM40) mRNA by in situ hybridization correlates with protein expression by immunohistochemistry and is associated with tumor progression. Virchows Arch 470, 91–98 (2017). https://doi.org/10.1007/s00428-016-2048-0

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  • DOI: https://doi.org/10.1007/s00428-016-2048-0

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