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Altered cytoplasmic-to-nuclear ratio of survivin is a prognostic indicator in breast cancer

Brennan, Donal J; Rexhepaj, Elton; O'Brien, Sallyann L; McSherry, Elaine; O'Connor, Darran P; Fagan, Ailis; Culhane, Aedin C; Higgins, Desmond G; Jirstrom, Karin and Millikan, Robert C, et al. (2008) In Clinical Cancer Research 14(9). p.2681-2689
Abstract
Purpose: Survivin (BIRC5) is a promising tumor biomarker. Conflicting data exist on its prognostic effect in breast cancer. These data may at least be partly due to the manual interpretation of immunohistochemical staining, especially as survivin can be located in both the nucleus and cytoplasm. Quantitative determination of survivin expression using image analysis offers the opportunity to develop alternative scoring models for survivin immunohistochemistry. Here, we present such a model. Experimental Design: A breast cancer tissue microarray containing 102 tumors was stained with an anti-survivin antibody. Whole-slide scanning was used to capture high-resolution images. These images were analyzed using automated algorithms to quantify... (More)
Purpose: Survivin (BIRC5) is a promising tumor biomarker. Conflicting data exist on its prognostic effect in breast cancer. These data may at least be partly due to the manual interpretation of immunohistochemical staining, especially as survivin can be located in both the nucleus and cytoplasm. Quantitative determination of survivin expression using image analysis offers the opportunity to develop alternative scoring models for survivin immunohistochemistry. Here, we present such a model. Experimental Design: A breast cancer tissue microarray containing 102 tumors was stained with an anti-survivin antibody. Whole-slide scanning was used to capture high-resolution images. These images were analyzed using automated algorithms to quantify the staining. Results: Increased nuclear, but not cytoplasmic, survivin was associated with a reduced overall survival (OS; P = 0.038) and disease-specific survival (P = 0.0015). A high cytoplasmicto-nuclear ratio (CNR) of survivin was associated with improved OS (P = 0.005) and disease-specific survival (P = 0.05). Multivariate analysis revealed that the survivin CNR was an independent predictor of CIS (hazard ratio, 0.09; 95% confidence interval, 0.01-0.76; P = 0.027). A survivin CNR of >5 correlated positively with estrogen receptor (P = 0.019) and progesterone receptor (P = 0.033) levels, whereas it was negatively associated with Ki-67 expression (P = 0.04), p53 status (P = 0.005), and c-myc amplification (P = 0.016). Conclusion: Different prognostic information is supplied by nuclear and cytoplasmic survivin in breast cancer. Nuclear survivin is a poor prognostic marker in breast cancer. Moreover, CNR of survivin, as determined by image analysis, is an independent prognostic factor. (Less)
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Clinical Cancer Research
volume
14
issue
9
pages
2681 - 2689
publisher
American Association for Cancer Research
external identifiers
  • wos:000255616300021
  • scopus:50249145879
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-07-1760
language
English
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yes
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6b8db3c8-ffa1-44a1-83e6-dc602555666b (old id 1204818)
date added to LUP
2008-09-18 11:15:26
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2017-05-21 03:45:14
@article{6b8db3c8-ffa1-44a1-83e6-dc602555666b,
  abstract     = {Purpose: Survivin (BIRC5) is a promising tumor biomarker. Conflicting data exist on its prognostic effect in breast cancer. These data may at least be partly due to the manual interpretation of immunohistochemical staining, especially as survivin can be located in both the nucleus and cytoplasm. Quantitative determination of survivin expression using image analysis offers the opportunity to develop alternative scoring models for survivin immunohistochemistry. Here, we present such a model. Experimental Design: A breast cancer tissue microarray containing 102 tumors was stained with an anti-survivin antibody. Whole-slide scanning was used to capture high-resolution images. These images were analyzed using automated algorithms to quantify the staining. Results: Increased nuclear, but not cytoplasmic, survivin was associated with a reduced overall survival (OS; P = 0.038) and disease-specific survival (P = 0.0015). A high cytoplasmicto-nuclear ratio (CNR) of survivin was associated with improved OS (P = 0.005) and disease-specific survival (P = 0.05). Multivariate analysis revealed that the survivin CNR was an independent predictor of CIS (hazard ratio, 0.09; 95% confidence interval, 0.01-0.76; P = 0.027). A survivin CNR of >5 correlated positively with estrogen receptor (P = 0.019) and progesterone receptor (P = 0.033) levels, whereas it was negatively associated with Ki-67 expression (P = 0.04), p53 status (P = 0.005), and c-myc amplification (P = 0.016). Conclusion: Different prognostic information is supplied by nuclear and cytoplasmic survivin in breast cancer. Nuclear survivin is a poor prognostic marker in breast cancer. Moreover, CNR of survivin, as determined by image analysis, is an independent prognostic factor.},
  author       = {Brennan, Donal J and Rexhepaj, Elton and O'Brien, Sallyann L and McSherry, Elaine and O'Connor, Darran P and Fagan, Ailis and Culhane, Aedin C and Higgins, Desmond G and Jirstrom, Karin and Millikan, Robert C and Landberg, Göran and Duffy, Michael J and Hewitt, Stephen M and Gallaghe, William M},
  issn         = {1078-0432},
  language     = {eng},
  number       = {9},
  pages        = {2681--2689},
  publisher    = {American Association for Cancer Research},
  series       = {Clinical Cancer Research},
  title        = {Altered cytoplasmic-to-nuclear ratio of survivin is a prognostic indicator in breast cancer},
  url          = {http://dx.doi.org/10.1158/1078-0432.CCR-07-1760},
  volume       = {14},
  year         = {2008},
}