Survivin mRNA Levels Are Associated With Biology of Disease ... : Journal of Pediatric Hematology/Oncology (original) (raw)

Original Articles

Survivin mRNA Levels Are Associated With Biology of Disease and Patient Survival in Neuroblastoma: A Report From the Children's Oncology Group

Miller, Michal A. MD*; Ohashi, Kensuke MD*; Zhu, Xiaoyan*; McGrady, Patrick PhD†; London, Wendy B. PhD†; Hogarty, Michael MD‡; Sandler, Anthony D. MD*

*Departments of Surgery and Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA

†Department of Statistics, University of Florida and Children's Oncology Group (COG)

‡Division of Oncology, Children’s Hospital of Philadelphia, Philadelphia, PA

Reprints: Anthony D. Sandler, MD, Division of Pediatric Surgery, Department of Surgery, University of Iowa Health Care, 200 Hawkins Drive, Iowa City, IA 52242 (e-mails: [email protected]; [email protected]).

Supported in part by grants from NIH (T-32 HL07344, COG grant U10 CA98413) and Michael C. Sandler. A complete listing of grant support for research conducted by CCG and POG before initiation of the COG grant in 2003 is available online at: http://www.childrensoncologygroup.org/admin/grantinfo.htm.

Received for publication October 27, 2005; accepted April 18, 2006

Journal of Pediatric Hematology/Oncology 28(7):p 412-417, July 2006. | DOI: 10.1097/01.mph.0000212937.00287.e5

Abstract

Alterations in apoptotic mechanisms favoring cell survival may be vital for modifying tumor behavior. Survivin, an inhibitor of apoptosis, and caspase 8, a proapoptotic enzyme, are key players in cellular apoptotic mechanisms. We investigated whether the levels of survivin and caspase 8 and the ratio between these 2 apoptotic factors correlate with tumor biology and predicts outcome in patients with neuroblastoma. Survivin and caspase 8 levels were quantified in 38 primary tumor specimens and analyzed individually and in relation to each other. High survivin expression and high survivin:caspase 8 ratios were associated with MYCN amplification, unfavorable histology, and high-risk group of disease (P<0.0008). High survivin mRNA levels were associated with worse overall survival (_P_=0.02) although the median follow up was only 22.6 months with a range of 1 day to 3.3 years. Low caspase 8 expression was associated with stage 4 disease, high-risk group, MYCN amplification, and unfavorable histology. Although the survivin:caspase 8 ratio was associated with these risk factors, the ratio did not improve the predictive value of survivin alone in this small series. Quantifying multiple apoptotic genes in neuroblastoma may supplement current risk stratification. Moreover, categorizing aberrant apoptotic gene expression in neuroblastoma may translate into novel therapeutic targets.