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A Novel Anti-Apoptosis Gene: Re-expression of Survivin Messenger RNA as a Prognosis Marker in Non–Small-Cell Lung Cancers

From the Laboratory of Molecular Biology of Cancer, Medical Oncology Service, and Thoracic Surgery Service, University Hospital Germans Trias i Pujol, Badalona; Medical Oncology Service and Thoracic Surgery Service, University Hospital Vall d'Hebron, Barcelona; and Statistical Department, School of Medicine, Free University of Madrid, Madrid, Spain.

Address reprint requests to Rafael Rosell, MD, Medical Oncology Service, Hospital Germans Trias i Pujol, Crtra Canyet, s/n, 08916 Badalona (Barcelona), Spain; email rrosell{at}ns.hugtip.scs.es

PURPOSE: The survivin gene is a novel apoptosis inhibitor, related to the baculovirus gene, which is believed to play a pivotal role in fetal development and in cancer. We hypothesised that survivin would be expressed in tumors of patients with non–small-cell lung cancer (NSCLC), and we attempted to determine the influence of survivin re-expression on clinical outcome in patients with up to stage IIIA NSCLC who had undergone radical surgery.

METHODS: We designed a reverse transcriptase polymerase chain reaction (RT-PCR) assay to study the expression of the survivin gene in 83 NSCLC tumor samples and compared the results with relevant clinical and pathologic data.

RESULTS: The RT-PCR identified survivin gene transcript in 71 (85.5%) of the tumor samples and in only 10 (12%) of the paired, histopathologically normal lung samples. There was no relationship between histologic subtype (squamous v nonsquamous) and survivin gene expression. The 12 patients without survivin expression had significantly better overall survival than the 71 patients with survivin expression (P = .01 by univariate analysis; relative risk, 2.1). There was no significant correlation between survivin expression and age, sex, cigarette smoking, histologic subtype, tumor differentiation, tumor size, or the presence of mediastinal lymph node metastases in surgical specimens.

CONCLUSION: The survivin gene was expressed in a vast majority of NSCLC tumors. We conclude that survivin transcript is a defining diagnostic marker for NSCLC that may also yield prognostic information and, as an apoptosis inhibitor, be an important target in cancer therapy.

Research was conducted at Hospital Germans Trias i Pujol, Badalona, and supported in part by grant no. 97/1064 from the Fondo Investigaciones Sanitarias de la Seguridad Social and a grant from Rhône-Poulenc Rorer, Madrid, Spain.

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				M MILLER, D SMITH, A WINDSOR, A KESSLING, A I SARELA, S M FARMERY, and P J GUILLOU Survivin gene expression and prognosis in recurrent colorectal cancer Reply Gut, January 1, 2001; 48(1): 137 - 138. [Full Text] [PDF]

				C. Adida, C. Haioun, P. Gaulard, E. Lepage, P. Morel, J. Briere, H. Dombret, F. Reyes, J. Diebold, C. Gisselbrecht, et al. Prognostic significance of survivin expression in diffuse large B-cell lymphomas Blood, September 1, 2000; 96(5): 1921 - 1925. [Abstract] [Full Text] [PDF]

				R. A. Olie, A. P. Simoes-Wust, B. Baumann, S. H. Leech, D. Fabbro, R. A. Stahel, and U. Zangemeister-Wittke A Novel Antisense Oligonucleotide Targeting Survivin Expression Induces Apoptosis and Sensitizes Lung Cancer Cells to Chemotherapy Cancer Res., June 1, 2000; 60(11): 2805 - 2809. [Abstract] [Full Text] [PDF]

				D. Grossman, P. J. Kim, J. S. Schechner, and D. C. Altieri Inhibition of melanoma tumor growth in vivo by survivin targeting PNAS, January 16, 2001; 98(2): 635 - 640. [Abstract] [Full Text] [PDF]