Validation of cytoplasmic-to-nuclear ratio of survivin as an indicator of improved prognosis in breast cancer
Rexhepaj, Elton ; Jirström, Karin LU
; O'Connor, Darran P.
; O'Brien, Sallyann L.
; Landberg, Göran
LU
; Duffy, Michael J.
; Brennan, Donal J.
and Gallagher, William M.
(2010)
In BMC Cancer
10.
- Abstract
- Background: Conflicting data exist regarding the prognostic and predictive impact of survivin (BIRC5) in breast cancer. We previously reported survivin cytoplasmic-to-nuclear ratio (CNR) as an independent prognostic indicator in breast cancer. Here, we validate survivin CNR in a separate and extended cohort. Furthermore, we present new data suggesting that a low CNR may predict outcome in tamoxifen-treated patients. Methods: Survin expression was assessed using immunhistochemistry on a breast cancer tissue microarray (TMA) containing 512 tumours. Whole slide digital images were captured using an Aperio XT scanner. Automated image analysis was used to identify tumour from stroma and then to quantify tumour-specific nuclear and cytoplasmic... (More)
- Background: Conflicting data exist regarding the prognostic and predictive impact of survivin (BIRC5) in breast cancer. We previously reported survivin cytoplasmic-to-nuclear ratio (CNR) as an independent prognostic indicator in breast cancer. Here, we validate survivin CNR in a separate and extended cohort. Furthermore, we present new data suggesting that a low CNR may predict outcome in tamoxifen-treated patients. Methods: Survin expression was assessed using immunhistochemistry on a breast cancer tissue microarray (TMA) containing 512 tumours. Whole slide digital images were captured using an Aperio XT scanner. Automated image analysis was used to identify tumour from stroma and then to quantify tumour-specific nuclear and cytoplasmic survivin. A decision tree model selected using a 10-fold cross-validation approach was used to identify prognostic subgroups based on nuclear and cytoplasmic survivin expression. Results: Following optimisation of the staining procedure, it was possible to evaluate survivin protein expression in 70.1% (n = 359) of the 512 tumours represented on the TMA. Decision tree analysis predicted that nuclear, as opposed to cytoplasmic, survivin was the most important determinant of overall survival (OS) and breast cancer-specific survival (BCSS). The decision tree model confirmed CNR of 5 as the optimum threshold for survival analysis. Univariate analysis demonstrated an association between a high CNR (>5) and a prolonged BCSS (HR 0.49, 95% CI 0.29-0.81, p = 0.006). Multivariate analysis revealed a high CNR (>5) was an independent predictor of BCSS (HR 0.47, 95% CI 0.27-0.82, p = 0.008). An increased CNR was associated with ER positive (p = 0.045), low grade (p = 0.007), Ki-67 (p = 0.001) and Her2 (p = 0.026) negative tumours. Finally, a high CNR was an independent predictor of OS in tamoxifen-treated ER-positive patients (HR 0.44, 95% CI 0.23-0.87, p = 0.018). Conclusion: Using the same threshold as our previous study, we have validated survivin CNR as a marker of good prognosis in breast cancer in a large independent cohort. These findings provide robust evidence of the importance of survivin CNR as a breast cancer biomarker, and its potential to predict outcome in tamoxifen-treated patients. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1773531
- author
- Rexhepaj, Elton
; Jirström, Karin
LU
; O'Connor, Darran P.
; O'Brien, Sallyann L.
; Landberg, Göran
LU
; Duffy, Michael J.
; Brennan, Donal J.
and Gallagher, William M.
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- BMC Cancer
- volume
- 10
- publisher
- BioMed Central (BMC)
- external identifiers
-
- wos:000285183300001
- scopus:78549255596
- pmid:21092276
- ISSN
- 1471-2407
- DOI
- 10.1186/1471-2407-10-639
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pathology (Malmö) (013031000), Pathology, (Lund) (013030000)
- id
- c7ae1605-4a0f-4ebe-ba52-df00fa990ae0 (old id 1773531)
- date added to LUP
- 2016-04-01 14:51:54
- date last changed
- 2024-01-29 02:53:29
@article{c7ae1605-4a0f-4ebe-ba52-df00fa990ae0,
abstract = {{Background: Conflicting data exist regarding the prognostic and predictive impact of survivin (BIRC5) in breast cancer. We previously reported survivin cytoplasmic-to-nuclear ratio (CNR) as an independent prognostic indicator in breast cancer. Here, we validate survivin CNR in a separate and extended cohort. Furthermore, we present new data suggesting that a low CNR may predict outcome in tamoxifen-treated patients. Methods: Survin expression was assessed using immunhistochemistry on a breast cancer tissue microarray (TMA) containing 512 tumours. Whole slide digital images were captured using an Aperio XT scanner. Automated image analysis was used to identify tumour from stroma and then to quantify tumour-specific nuclear and cytoplasmic survivin. A decision tree model selected using a 10-fold cross-validation approach was used to identify prognostic subgroups based on nuclear and cytoplasmic survivin expression. Results: Following optimisation of the staining procedure, it was possible to evaluate survivin protein expression in 70.1% (n = 359) of the 512 tumours represented on the TMA. Decision tree analysis predicted that nuclear, as opposed to cytoplasmic, survivin was the most important determinant of overall survival (OS) and breast cancer-specific survival (BCSS). The decision tree model confirmed CNR of 5 as the optimum threshold for survival analysis. Univariate analysis demonstrated an association between a high CNR (>5) and a prolonged BCSS (HR 0.49, 95% CI 0.29-0.81, p = 0.006). Multivariate analysis revealed a high CNR (>5) was an independent predictor of BCSS (HR 0.47, 95% CI 0.27-0.82, p = 0.008). An increased CNR was associated with ER positive (p = 0.045), low grade (p = 0.007), Ki-67 (p = 0.001) and Her2 (p = 0.026) negative tumours. Finally, a high CNR was an independent predictor of OS in tamoxifen-treated ER-positive patients (HR 0.44, 95% CI 0.23-0.87, p = 0.018). Conclusion: Using the same threshold as our previous study, we have validated survivin CNR as a marker of good prognosis in breast cancer in a large independent cohort. These findings provide robust evidence of the importance of survivin CNR as a breast cancer biomarker, and its potential to predict outcome in tamoxifen-treated patients.}},
author = {{Rexhepaj, Elton and Jirström, Karin and O'Connor, Darran P. and O'Brien, Sallyann L. and Landberg, Göran and Duffy, Michael J. and Brennan, Donal J. and Gallagher, William M.}},
issn = {{1471-2407}},
language = {{eng}},
publisher = {{BioMed Central (BMC)}},
series = {{BMC Cancer}},
title = {{Validation of cytoplasmic-to-nuclear ratio of survivin as an indicator of improved prognosis in breast cancer}},
url = {{https://lup.lub.lu.se/search/files/4208305/1787781.pdf}},
doi = {{10.1186/1471-2407-10-639}},
volume = {{10}},
year = {{2010}},
}