Significance of survivin mRNA expression in prognosis of neuroblastoma.
Neuroblastoma (NB) is the most common malignant solid tumor in childhood, and among all childhood malignancies is second in prevalence only to leukemia. In NB we need to both make an accurate diagnosis and rapidly analyze the expression of genetic prognostic factors such as MYCN, H-ras, and trkA. Moreover, it has recently become important to analyze the expression of survivin mRNA, a member of the inhibitor of apoptosis protein family. Expression of the survivin gene is related to tumorigenesis and inhibition of apoptosis in some malignant tumors. We investigated its expression by reverse transcription-polymerase chain reaction (RT-PCR) in NB cell lines (SK-N-SH, NB-39, and IMR-32), two normal blood cell samples, and 13 clinical NB tumor samples. All three NB cell lines had high levels of mRNA expression for this gene, but normal blood cells had no expression. We detected expression of survivin mRNA in 7 of the 13 NB tumor samples (54%). Two NB patients were in stage I disease, 6 in stage II, and 5 in stage IV(A). Quantitative analysis by RT-PCR revealed that the ratio between survivin mRNA and human glyceraldehyde-3-phosphate dehydrogenase (h-GAPDH) mRNA was very low in stages I and II (0-0.017). In contrast, in advanced NBs (stage IV(A)) the ratio was much higher (0-0.050). The prognoses of the three patients in the advanced stage who had high ratios of expression were poor. A high level of expression of survivin mRNA indicates a high grade of malignancy, high likelihood of recurrence, and poor prognosis.