Somatostatin receptor type 2 gene expression in neuroblastoma, measured by competitive RT-PCR, is related to patient survival and to somatostatin receptor imaging by indium -111-pentetreotide.
BACKGROUND
We previously reported that human neuroblastoma cell lines and primary neuroblastoma tumors expressed a variable amount of mRNA for type 2 somatostatin (sst2) receptor gene. We also found that high level of sst2 expression were positively related to patient survival.


METHODS
We studied retrospectively 49 primary neuroblastomas. To detect and measure sst2 mRNA expression we developed a quantitative RT-PCR based on competitive PCR. When possible the number of MYCN copies was also measured with competitive PCR. RESULTS;. We found that the lowest level of sst2 mRNA was detected in advanced stages of neuroblastomas (stage IV) when compared with the other stages (P< 0.005). Patients with high levels of sst2 expression (>7 x 10(7) molecules/microg RNA) had a cumulative survival better than those with low sst2 expression (P < 0.0005). This predictive independent value of sst2 (P= 0.005) is retained after stratification for N-myc amplification. Finally we verified that the ex vivo sst2 gene expression in tumor samples was positively related (P < 0.01) to the in vivo semiquantitative determination of sst2 protein, assessed by 111In-pentetreotide imaging.


CONCLUSIONS
Our data indicate that the measurement of sst2 mRNA measurement could represent a relevant tool in the prediction of neuroblastoma outcome, independently from MYCN amplification.
Orlando
C
C
Dep of Clinical Physiopathology, University of Florence, Italy. c.orlando@dfc.unifi.it
Raggi
C C
CC
Bagnoni
L
L
Sestini
R
R
Briganti
V
V
La Cava
G
G
Bernini
G
G
Tonini
G P
GP
Pazzagli
M
M
Serio
M
M
Maggi
M
M
D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D007205:Indium Radioisotopes; D007223:Infant; D007231:Infant, Newborn; D015993:Life Tables; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D009447:Neuroblastoma / Q000737:chemistry / Q000000981:diagnostic imaging / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000031:analogs & derivatives; D016019:Survival Analysis; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D007205:Indium Radioisotopes; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; D013004:Somatostatin; C093733:somatostatin receptor 2; C081788:pentetreotide