Remke Marc, Hering Esther, Gerber Nicolas U, Kool Marcel, Sturm Dominik, Rickert Christian H, Gerß Joachim, Schulz Stefan, Hielscher Thomas, Hasselblatt Martin, Jeibmann Astrid, Hans Volkmar, Ramaswamy Vijay, Taylor Michael D, Pietsch Torsten, Rutkowski Stefan, Korshunov Andrey, Monoranu Carmelia-Maria, Frühwald Michael C
Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumor Research Centre, Program in Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Childs Nerv Syst. 2013 Aug;29(8):1253-62. doi: 10.1007/s00381-013-2142-4. Epub 2013 May 16.
Neuroectodermal tumors in general demonstrate high and dense expression of the somatostatin receptor subtype 2 (sst₂). It controls proliferation of both normal and neoplastic cells. sst₂ has thus been suggested as a therapeutic target and prognostic marker for certain malignancies.
To assess global expression patterns of sst 2 mRNA, we evaluated normal (n = 353) and tumor tissues (n = 340) derived from previously published gene expression profiling studies. These analyses demonstrated specific upregulation of sst 2 mRNA in medulloblastoma (p < 0.001). sst₂ protein was investigated by immunohistochemistry in two independent cohorts.
Correlation of sst₂ protein expression with clinicopathological variables revealed significantly higher levels in medulloblastoma (p < 0.05) compared with CNS-PNET, ependymoma, or pilocytic astrocytoma. The non-SHH medulloblastoma subgroup tumors showed particularly high expression of sst₂, when compared to other tumors and normal tissues. Furthermore, we detected a significant survival benefit in children with tumors exhibiting high sst₂ expression (p = 0.02) in this screening set. A similar trend was observed in a validation cohort including 240 independent medulloblastoma samples.
sst₂ is highly expressed in medulloblastoma and deserves further evaluation in the setting of prospective trials, given its potential utility as a prognostic marker and a therapeutic target.
一般来说，神经外胚层肿瘤表现出生长抑素受体2型（sst₂）的高表达和密集表达。它控制正常细胞和肿瘤细胞的增殖。因此，sst₂已被建议作为某些恶性肿瘤的治疗靶点和预后标志物。
为了评估sst₂ mRNA的整体表达模式，我们评估了来自先前发表的基因表达谱研究的正常组织（n = 353）和肿瘤组织（n = 340）。这些分析表明，髓母细胞瘤中sst₂ mRNA有特异性上调（p < 0.001）。通过免疫组织化学在两个独立队列中研究了sst₂蛋白。
sst₂蛋白表达与临床病理变量的相关性显示，与中枢神经系统原始神经外胚层肿瘤、室管膜瘤或毛细胞型星形细胞瘤相比，髓母细胞瘤中的sst₂蛋白水平显著更高（p < 0.05）。与其他肿瘤和正常组织相比，非SHH髓母细胞瘤亚组肿瘤显示出特别高的sst₂表达。此外，在该筛查组中，我们检测到sst₂高表达的肿瘤患儿有显著的生存获益（p = 0.02）。在一个包含240个独立髓母细胞瘤样本的验证队列中也观察到了类似趋势。
sst₂在髓母细胞瘤中高度表达，鉴于其作为预后标志物和治疗靶点的潜在效用，值得在前瞻性试验中进一步评估。
