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 language | English |
|---|---|
| Pages (from-to) | 976-987 |
| Number of pages | 12 |
| Journal | Histopathology |
| Volume | 76 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published or Issued - 1 Jun 2020 |
Keywords
- apolipoprotein D
- breast cancer
- prognosis
- survival outcome
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Histology
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}
In: Histopathology, Vol. 76, No. 7, 01.06.2020, p. 976-987.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Elevated levels of tumour apolipoprotein D independently predict poor outcome in breast cancer patients
AU - Jankovic-Karasoulos, Tanja
AU - Bianco-Miotto, Tina
AU - Butler, Miriam S.
AU - Butler, Lisa M.
AU - McNeil, Catriona M.
AU - O’Toole, Sandra A.
AU - Millar, Ewan K.A.
AU - Sakko, Andrew J.
AU - Ruiz, Alexandra I.
AU - Birrell, Stephen N.
AU - Sutherland, Robert L.
AU - Hickey, Theresa E.
AU - Tilley, Wayne D.
AU - Ricciardelli, Carmela
N1 - Funding Information: This work was supported by grants from the National Health and Medical Research Council of Australia (NHMRC) (ID 1130077 and 1084416 to W. D. Tilley and T. E. Hickey; Program Grant 535903 to E. K. A. Millar, S. A. O’Toole, and R. L. Sutherland; Fellowship 427601 to R. L. Sutherland), Cancer Australia (ID 1107170 WDT, TEH), and Susan G. Komen for the Cure (ID BCTR0601118 to W. D. Tilley, S. N. Birrell, and T. Bianco‐Miotto). L. M. Butler is supported by a Future Fellowship from the Australian Research Council (FT130101004), and a Principal Cancer Research Fellowship produced with the financial and other support of Cancer Council South Australia’s Beat Cancer Project on behalf of its donors and the State Government of South Australia through the Department of Health. C. M. McNeil was supported by an NHMRC Postgraduate Medical and Dental Scholarship (2004‐2007) and a Cancer Institute NSW Scholarship (2005‐2007). S. O. O’Toole is funded by the National Breast Cancer Foundation Practitioner Fellowship (16‐006). W. D. Tilley is also supported by a grant from the National Breast Cancer Foundation (PS‐15‐041). C. Ricciardelli was supported by the Hilda Farmer Research Fellowship (University of Adelaide Faculty of Health Sciences), and is currently supported by the Lin Huddleston Ovarian Cancer Fellowship funded by the Cancer Council South Australia and the Adelaide Medical School, University of Adelaide. T. Bianco‐Miotto was supported by the NHMRC Peter Doherty Fellowship (#349556). T. E. Hickey held a Florey Career Development Fellowship from the Royal Adelaide Hospital Research Foundation, and is supported by an NBCF Fellowship (IIRS‐19‐009) and the University of Adelaide. Additional support was provided by the Cancer Institute of New South Wales (Translational Program Grant 10/TPG/1‐04 to R. L. Sutherland, E. K. A. Millar, and S. A. O’Toole; Sydney Catalyst Translational Research Centre 11/TRC/1‐02 to R. L. Sutherland; Fellowship 10/CRF/1‐07 to S. A. O’Toole), the Australia and New Zealand Breast Cancer Trials Group (R. L. Sutherland and S. A. O’Toole), the Australian Cancer Research Foundation (R. L. Sutherland), the Sydney Breast Cancer Foundation (S. A. O’Toole), the RT Hall Trust (R. L. Sutherland), and the Petre Foundation (R. L. Sutherland). The funders had no role in study design, data collection, and analysis, the decision to publish, or the preparation of the manuscript. Funding Information: This work was supported by grants from the National Health and Medical Research Council of Australia (NHMRC) (ID 1130077 and 1084416 to W. D. Tilley and T. E. Hickey; Program Grant 535903 to E. K. A. Millar, S. A. O?Toole, and R. L. Sutherland; Fellowship 427601 to R. L. Sutherland), Cancer Australia (ID 1107170 WDT, TEH), and Susan G. Komen for the Cure (ID BCTR0601118 to W. D. Tilley, S. N. Birrell, and T. Bianco-Miotto). L. M. Butler is supported by a Future Fellowship from the Australian Research Council (FT130101004), and a Principal Cancer Research Fellowship produced with the financial and other support of Cancer Council South Australia?s Beat Cancer Project on behalf of its donors and the State Government of South Australia through the Department of Health. C. M. McNeil was supported by an NHMRC Postgraduate Medical and Dental Scholarship (2004-2007) and a Cancer Institute NSW Scholarship (2005-2007). S. O. O?Toole is funded by the National Breast Cancer Foundation Practitioner Fellowship (16-006). W. D. Tilley is also supported by a grant from the National Breast Cancer Foundation (PS-15-041). C. Ricciardelli was supported by the Hilda Farmer Research Fellowship (University of Adelaide Faculty of Health Sciences), and is currently supported by the Lin Huddleston Ovarian Cancer Fellowship funded by the Cancer Council South Australia and the Adelaide Medical School, University of Adelaide. T. Bianco-Miotto was supported by the NHMRC Peter Doherty Fellowship (#349556). T. E. Hickey held a Florey Career Development Fellowship from the Royal Adelaide Hospital Research Foundation, and is supported by an NBCF Fellowship (IIRS-19-009) and the University of Adelaide. Additional support was provided by the Cancer Institute of New South Wales (Translational Program Grant 10/TPG/1-04 to R. L. Sutherland, E. K. A. Millar, and S. A. O?Toole; Sydney Catalyst Translational Research Centre 11/TRC/1-02 to R. L. Sutherland; Fellowship 10/CRF/1-07 to S. A. O?Toole), the Australia and New Zealand Breast Cancer Trials Group (R. L. Sutherland and S. A. O?Toole), the Australian Cancer Research Foundation (R. L. Sutherland), the Sydney Breast Cancer Foundation (S. A. O?Toole), the RT Hall Trust (R. L. Sutherland), and the Petre Foundation (R. L. Sutherland). The funders had no role in study design, data collection, and analysis, the decision to publish, or the preparation of the manuscript.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
KW - apolipoprotein D
KW - breast cancer
KW - prognosis
KW - survival outcome
UR - http://www.scopus.com/inward/record.url?scp=85084650127&partnerID=8YFLogxK
U2 - 10.1111/his.14081
DO - 10.1111/his.14081
M3 - Article
C2 - 31994214
AN - SCOPUS:85084650127
SN - 0309-0167
VL - 76
SP - 976
EP - 987
JO - Histopathology
JF - Histopathology
IS - 7
ER -