Orlando C, Raggi C C, Bagnoni L, Sestini R, Briganti V, La Cava G, Bernini G, Tonini G P, Pazzagli M, Serio M, Maggi M
Dep of Clinical Physiopathology, University of Florence, Italy.
Med Pediatr Oncol. 2001 Jan;36(1):224-6. doi: 10.1002/1096-911X(20010101)36:1<224::AID-MPO1054>3.0.CO;2-#.
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.
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.
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.
我们之前报道过人神经母细胞瘤细胞系和原发性神经母细胞瘤肿瘤表达了数量可变的2型生长抑素(sst2)受体基因的mRNA。我们还发现高水平的sst2表达与患者生存率呈正相关。
我们回顾性研究了49例原发性神经母细胞瘤。为了检测和测量sst2 mRNA表达,我们基于竞争性PCR开发了一种定量RT-PCR。在可能的情况下,还通过竞争性PCR测量MYCN拷贝数。结果:我们发现与其他阶段相比,在神经母细胞瘤晚期(IV期)检测到的sst2 mRNA水平最低(P<0.005)。sst2表达水平高(>7×10⁷分子/μg RNA)的患者累积生存率优于sst2表达水平低的患者(P<0.0005)。在对N-myc扩增进行分层后,sst2的这种预测独立价值(P=0.005)得以保留。最后,我们证实肿瘤样本中的体外sst2基因表达与通过¹¹¹In-喷替肽显像评估的体内sst2蛋白半定量测定呈正相关(P<0.01)。
我们的数据表明,测量sst2 mRNA可能是预测神经母细胞瘤预后的一种相关工具,独立于MYCN扩增。