title: High survivin mRNA expression is a predictor of poor prognosis in breast cancer: a comparative study at the mRNA and protein level.
abstract: BACKGROUND
  Survivin plays a key role in the initiation and progression of breast cancer. However, its prognostic relevance to breast cancer patients has long been a matter of debate. The purpose of this study was to examine the expression of survivin and its role in predicting clinical outcome in a series of human breast cancer cases both at the mRNA and protein level.
  
  
  METHODS
  Formalin-fixed paraffin-embedded tumor tissues from 245 female patients with invasive breast cancer and 13 patients with ductal carcinoma in situ were examined for survivin mRNA by quantitative real-time RT-PCR (RT-qPCR). In addition, 237 of these tumors with invasive breast cancer were available for immunohistochemistry (IHC). The relationship between survivin status and clinicopathological characteristics and prognosis was evaluated.
  
  
  RESULTS
  RT-qPCR revealed that high levels of survivin mRNA were strongly associated with high nuclear grade, positive axillary lymph nodes, negative hormone receptor status, positive Her2 amplification, higher Ki67 labeling index, and presence of vascular invasion. In the Cox proportional regression model analysis, survivin mRNA was shown to be a significant univariate parameter for relapse-free survival (RFS), distant relapse-free survival (DRFS), and breast cancer-specific survival (BCSS) as well as a significant multivariate parameter for RFS, DRFS, and BCSS. In hormone receptor (HR)-positive/Her2-negative subtype cases, survivin mRNA expression was also an independent predictor in terms of DRFS. Immunohistochemically, positive staining was seen in the cytoplasm and/or nucleus of cancer cells, although this did not correlate with the mRNA level, and harbored no prognostic value.
  
  
  CONCLUSIONS
  High mRNA expression of survivin was an independent marker of poor prognosis both in the entire cohort and in the HR-positive/Her2-negative subtype, whereas the protein expression of survivin was not. These findings suggest that RT-qPCR can provide more reliable data than IHC in validating the prognostic significance of survivin for breast cancer patients.
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo Kumamoto, Kumamoto, 860-8556, Japan.
authors.forename: Chunsen
authors.initials: C
authors.lastname: Xu
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Yamamoto-Ibusuki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Satoko
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Saori
authors.initials: S
authors.lastname: Fujiwara
authors.forename: Keiichi
authors.initials: K
authors.lastname: Murakami
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Okumura
authors.forename: Lisa
authors.initials: L
authors.lastname: Yamaguchi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujiki
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Iwase
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger; D000077022:Survivin