J Breast Cancer.  2009 Dec;12(4):285-294. 10.4048/jbc.2009.12.4.285.

The Prognostic Significance of Survivin Expression in Breast Cancer

• Oh JW
• Yang WI
• Lee MJ
• Park S
• Park BW
• Lee KS

• KMID: 2175523
• DOI: http://doi.org/10.4048/jbc.2009.12.4.285

Abstract

PURPOSE
Survivin is a member of the inhibitors of apoptosis family. It has recently comes into the limelight as a promising tumor marker, but many previous reports have shown controversial results regarding the significance and prognostic value of a survivin expression. In this study we determined the correlation between the survivin expression and the conventional prognostic markers and we also investigated the outcomes according to the localization of the survivin expression. METHODS: Tissue microarray (TMA) blocks were made with formalin-fixed paraffin-embedded tissues from 185 breast cancer patients and the immunohistochemical staining was done using an anti-survivin antibody. Among these, 157 patients were available for a survivin expression. The conventional clinicopathologic features and overall survival were correlated with the localization of the survivin expression. RESULTS: Survivin was expressed in 101 breast cancers (64.3%). A higher cytoplasmic survivin expression were noted in the older group (p=0.003), in the node-negative cancers (p=0.012), in the earlier tumor stages (p=0.012) and in the cancers that had not been treated with adjuvant chemotherapy (p=0.014). On the contrary, a higher nuclear survivin expression was inversely correlated with an estrogen expression (p=0.006) and a progesterone receptor (p=0.043) expression. In terms of survival, a cytoplasmic expression was associated with improved overall survival (p=0.01) but a nuclear survivin expression was correlated with unfavorable overall survival (p=0.002). A high cytoplasmic to nuclear ratio of survivin was associated with improved overall survival (p=0.001) conversely, increased nuclear to cytoplasmic survivin ratio was correlated with unfavorable overall survival (p<0.0001). Multivariate analysis revealed that nuclear survivin expression (p=0.001) and high nuclear to cytoplasmic survivin ratio (p=0.012) were independent predictor of overall survival. CONCLUSION: Survivin is frequently expressed in primary breast cancer. A cytoplasmic survivin expression is a good prognostic predictor for patients with axillary node negative early breast cancers and a nuclear survivin expression is a worse independent predictor of overall survival for patients with axillary node positive breast cancers.

Keyword

Breast neoplasms; Prognostic factor; Survivin

MeSH Terms

Apoptosis
Breast
Breast Neoplasms
Chemotherapy, Adjuvant
Cytoplasm
Estrogens
Humans
Multivariate Analysis
Receptors, Progesterone
Estrogens
Receptors, Progesterone

Figure

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  Fig 1. Immunohistochemical staining results for survivin (DAB with hematoxylin counterstaining). (A) Nuclear staining of survivin (×200), (B) Cytoplasmic and nuclear staining of survivin (×200), (C) Cytoplasmic staining of survivin (×200) in invasive ductal carcinoma.

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  Fig 2. Kaplan-Meier survival estimates for positive and negative cases of breast cancer regarding (A) cytoplasmic survivin expression and (B) nuclear survivin expression.

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  Fig 3. Kaplan-Meier survival estimates for using a ratio of 2 as a cutoff. (A) cytoplasmic to nuclear survivin expression ratio and (B) nuclear to cytoplasmic survivin expression ratio.

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  Fig 4. Kaplan-Meier survival curve according to lymph node negative group (A) and lymph node positive group (B) categorized by cytoplasmic survivin expression.

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  Fig 5. Kaplan-Meier survival curve according to lymph node negative group (A) and lymph node positive group (B) categorized by nuclear survivin expression.

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  Fig 6. Kaplan-Meier survival curve according to TNM stage categorized by cytoplasmic survivin expression.

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  Fig 7. Kaplan-Meier survival curve according to TNM stage categorized by nuclear survivin expression.

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