TY - JOUR
T1 - Quantitative determination of sst2 gene expression in neuroblastoma tumor predicts patient outcome
AU - Raggi, Claudia Casini
AU - Maggi, Mario
AU - Renzi, Daniela
AU - Calabrò, Antonino
AU - Bagnoni, Maria Letizia
AU - Scaruffi, Paola
AU - Tonini, Gian Paolo
AU - Pazzagli, Mario
AU - De Bernardi, Bruno
AU - Bernini, Gabriella
AU - Serio, Mario
AU - Orlando, Claudio
PY - 2000
Y1 - 2000
N2 - Neuroblastoma (NB) is the most common pediatric neuroendocrine tumor, and it is characterized by a quite variable clinical course. We previously found a great variability in the expression of somatostatin receptor type 2 (sst2) in several human NB cell lines and primary tumors. In this report we investigated whether expression of sst2 is somehow related to clinical outcome. We performed a retrospective study on 54 patients with a maximum follow-up of 100 months. The concentration of specific messenger ribonucleic acid (mRNA) for sst2 was measured by competitive RT-PCR and validated, in a small subset of samples, by quantitative imaging of gene (in situ hybridization) and protein (immunohistochemistry) expression. We found that sst2 mRNA was variably expressed in all NB tumors (range, 2.5 x 105 to 8 x 109 molecules/μg RNA) with a relevant reduction in the more advanced stage (P <0.01). Analysis of Kaplan-Meier curves indicated that sst2 expression is positively related to the overall (P <0.0001) and event-free (P <0.0001) survival. Expression of sst2 was negatively related to tumor stage (P <0.02) and MYCN amplification (P <0.001), a poor prognostic factor. However, the prognostic information derived from sst2 is apparently independent from MYCN amplification, as assessed by stratifying sst2 values according to MYCN. In addition, the expression of sst2 was the only significant prognostic factor (P <0.02) when it was included in a multivariate model containing other well known prognostic factors such as age, stage, and MYCN amplification. Hence, we propose that sst2 expression represents a new prognostic marker for NB. The main clinical value of a quantitative measure of sst2 lies in its ability to detect patients at low risk, independently from other prognostic factor, including MYCN amplification.
AB - Neuroblastoma (NB) is the most common pediatric neuroendocrine tumor, and it is characterized by a quite variable clinical course. We previously found a great variability in the expression of somatostatin receptor type 2 (sst2) in several human NB cell lines and primary tumors. In this report we investigated whether expression of sst2 is somehow related to clinical outcome. We performed a retrospective study on 54 patients with a maximum follow-up of 100 months. The concentration of specific messenger ribonucleic acid (mRNA) for sst2 was measured by competitive RT-PCR and validated, in a small subset of samples, by quantitative imaging of gene (in situ hybridization) and protein (immunohistochemistry) expression. We found that sst2 mRNA was variably expressed in all NB tumors (range, 2.5 x 105 to 8 x 109 molecules/μg RNA) with a relevant reduction in the more advanced stage (P <0.01). Analysis of Kaplan-Meier curves indicated that sst2 expression is positively related to the overall (P <0.0001) and event-free (P <0.0001) survival. Expression of sst2 was negatively related to tumor stage (P <0.02) and MYCN amplification (P <0.001), a poor prognostic factor. However, the prognostic information derived from sst2 is apparently independent from MYCN amplification, as assessed by stratifying sst2 values according to MYCN. In addition, the expression of sst2 was the only significant prognostic factor (P <0.02) when it was included in a multivariate model containing other well known prognostic factors such as age, stage, and MYCN amplification. Hence, we propose that sst2 expression represents a new prognostic marker for NB. The main clinical value of a quantitative measure of sst2 lies in its ability to detect patients at low risk, independently from other prognostic factor, including MYCN amplification.
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M3 - Article
C2 - 11061551
AN - SCOPUS:0033756786
VL - 85
SP - 3866
EP - 3873
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 10
ER -