Elevated levels of tumour apolipoprotein D independently predict poor outcome in breast cancer patients

Tanja Jankovic-Karasoulos, Tina Bianco-Miotto, Miriam S. Butler, Lisa M. Butler, Catriona M. McNeil, Sandra A. O’Toole, Ewan K.A. Millar, Andrew J. Sakko, Alexandra I. Ruiz, Stephen N. Birrell, Robert L. Sutherland, Theresa E. Hickey, Wayne D. Tilley, Carmela Ricciardelli

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Abstract

Aims: Apolipoprotein D (ApoD) is a protein that is regulated by androgen and oestrogen, and is a major constituent of breast cysts. Although ApoD has been reported to be a marker of breast cancer, its prognostic importance in invasive breast cancer is unclear. The aim of this study was to investigate the relationship between ApoD protein expression, oestrogen receptor-α (ERα) expression and androgen receptor (AR) expression in predicting breast cancer outcome. Methods and results: ApoD levels were measured by the use of immunohistochemistry and video image analysis on tissue sections from a breast cancer cohort (n = 214). We assessed the associations of ApoD expression with disease-free survival (DFS), metastasis-free survival (MFS), and overall survival (OS). We also assessed the relationship between ApoD expression, AR expression and ERα expression in predicting OS. ApoD expression (>1% ApoD positivity) was found in 72% (154/214) of tissues. High ApoD positivity (≥20.7%, fourth quartile) was an independent predictor of MFS and OS, and conferred a 2.2-fold increased risk of developing metastatic disease and a 2.1-fold increased risk of breast cancer-related death. ApoD positivity was not associated with AR or ERα nuclear positivity. However, patients with (≥1%) ERα-positive cancers with low (<20.7%) ApoD positivity, or those showing high (≥78%) AR positivity and low (<20.7%) ApoD positivity had better OS than other patient groups. Conclusions: ApoD expression could be used to predict breast cancer prognosis independently of ERα and AR expression.

Original languageEnglish
Pages (from-to)976-987
Number of pages12
JournalHISTOPATHOLOGY
Volume76
Issue number7
DOIs
Publication statusPublished - Jun 2020
Externally publishedYes

Keywords

  • apolipoprotein D
  • breast cancer
  • prognosis
  • survival outcome

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    Jankovic-Karasoulos, T., Bianco-Miotto, T., Butler, M. S., Butler, L. M., McNeil, C. M., O’Toole, S. A., Millar, E. K. A., Sakko, A. J., Ruiz, A. I., Birrell, S. N., Sutherland, R. L., Hickey, T. E., Tilley, W. D., & Ricciardelli, C. (2020). Elevated levels of tumour apolipoprotein D independently predict poor outcome in breast cancer patients. HISTOPATHOLOGY, 76(7), 976-987. https://doi.org/10.1111/his.14081