Survivin expression impacts prognostically on NSCLC but not SCLC

Abstract

Survivin is expressed in lung cancer and in most cancer tissues and has a significant impact on prognosis. This work aimed to comparatively assess survivin expression and significance in Non-Small (NSCLC) and Small Cell Lung Cancers (SCLC). Sixty-five NSCLC and 35 SCLC samples were analyzed by semi-quantitative real-time RT-PCR. Survivin mRNA levels were significantly higher in tumors than in normal tissue, and in SCLC than in NSCLC samples. Immunohistochemistry and FISH analyses were performed in 59 and 26 tumor specimens, respectively. In SCLC survivin was only present in cytoplasm, while in some NSCLC cases it also showed nuclear or mixed patterns. FISH analysis did not disclose survivin gene amplification, except for one NSCLC case. Finally, 90 samples were genotyped for the -31G/C SNP of survivin promoter by direct sequencing; the -31G/C SNP genotype status showed a significant association only with nodal NSCLC metastasis, but not with survivin expression in any tumor group. A better prognosis was correlated to higher levels of survivin mRNA and to the presence of at least one G allele at -31 SNP in NSCLC, while these parameters did not correlate with overall survival in SCLC. Moreover, this SNP would appear to have no effect on the risk of lung cancer in our samples. The different prognostic role played by survivin in NSCLC and SCLC highlights the biological differences between these lung tumor histotypes and stresses the need to clarify the molecular pathways leading to their neoplastic transformation.