Nuclear survivin expression in mantle cell lymphoma is associated with cell proliferation and survival

Am J Pathol. 2004 Feb;164(2):501-10. doi: 10.1016/S0002-9440(10)63140-9.


Survivin is a member of the inhibitor of apoptosis protein family that is expressed in G2/M phase. Survivin is overexpressed and associated with parameters of poor prognosis in different human tumors. The role of survivin in the pathogenesis of mantle cell lymphoma (MCL) was examined in a series of typical and blastoid tumors. Survivin was detected as a nuclear pattern in a variable number of tumor cells. Mitotic figures were always positive with a strong delineation of the chromosomes. Western blot analysis confirmed the presence of survivin only in nuclear fractions. Protein expression detected by immunohistochemistry correlated with mRNA levels analyzed by quantitative real-time reverse transcription-polymerase chain reaction (P < 0.0001). Survivin expression levels were higher in blastoid MCL variants (P < 0.0001) and were associated with the proliferative activity (P = 0.001), but not with the ploidy status of the tumors. The number of apoptotic cells was independent of survivin or Ki-67 expression. Overall survival was significantly shorter in patients with high survivin expression. However, in a multivariate analysis, proliferative index was a better predictor of survival than survivin score. These findings indicate that survivin is commonly expressed in MCL with a nuclear and mitotic pattern. The expression levels are strongly associated with the proliferative activity of the tumors and the survival of the patients, suggesting a potential role in cell cycle regulation and tumor progression.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology
  • Blotting, Western
  • Cell Cycle / physiology
  • Cell Division / physiology
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Survival / physiology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Inhibitor of Apoptosis Proteins
  • Lymphoma, Mantle-Cell / metabolism*
  • Lymphoma, Mantle-Cell / mortality
  • Microtubule-Associated Proteins / biosynthesis*
  • Neoplasm Proteins
  • Palatine Tonsil / metabolism
  • Palatine Tonsil / pathology
  • Ploidies
  • Prognosis
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survivin


  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • Survivin