Alexiou George A, Vartholomatos George, Stefanaki Kalliopi, Patereli Amalia, Dova Lefkothea, Karamoutsios Achilleas, Lallas George, Sfakianos George, Moschovi Maria, Prodromou Neofytos
Department of Neurosurgery, Children's Hospital "Agia Sofia," Athens;
J Neurosurg Pediatr. 2013 Nov;12(5):452-7. doi: 10.3171/2013.7.PEDS1376. Epub 2013 Aug 30.
Medulloblastoma (MB) is the most common malignant brain tumor in children. Heat shock proteins (HSPs) comprise a superfamily of proteins that serve as molecular chaperones and are overexpressed in a wide range of human cancers. The purpose of the present study was to investigate the expression of HSP27 (pSer(82)), HSP27 (pSer(15)), HSP40, HSP60, HSP70, HSP90-α, Akt, and phospho-Akt by multiplex bead array assay of MBs. The results of HSP and Akt expression were correlated with MB subtype; immunohistochemical expression of Ki-67 index, bcl-2, and p53; and patients' prognosis.
The authors retrospectively evaluated 25 children with MB who underwent surgery. Immunohistochemical analysis of Ki-67, p53, and bcl-2 expression was performed in all cases. By using multiplex bead array assay, a simultaneous detection of HSP27 (pSer(82)), HSP27 (pSer(15)), HSP40, HSP60, HSP70, HSP90-α, Akt, and phospho-Akt was performed.
Medulloblastoma with extensive nodularity had significantly lower HSP27 (pSer(15)) expression (p = 0.039) but significantly higher HSP60 expression (p = 0.021) than classic MB. Large-cell MB had significantly higher HSP70 expression (p = 0.028) than classic MB. No significant difference was found between HSP27 (pSer(82)), HSP40, HSP90-α, Akt, or phospho-Akt expression and MB subtype. Large-cell MBs had significantly higher Ki-67 index compared with classic MBs (p = 0.033). When analyzing all MBs, there was a significant negative correlation between HSP27 (pSer(15)) and Ki-67 index (r = -0.475, p = 0.016); a significant positive correlation between HSP70 expression and Ki-67 index (r = 0.407, p = 0.043); and a significant positive correlation between HSP70 expression and bcl-2 index (r = 0.491, p = 0.023). Patients with large-cell MB had a worse survival than those with classic MB, but the difference did not reach statistical significance (p = 0.076).
A substantial expression of several HSPs in MB was observed. Given that HSPs represent an attractive strategy for anticancer therapy, further studies, involving larger series of patients, are obviously necessary to clarify the relationship of HSPs with tumor aggressiveness and prognosis.
髓母细胞瘤（MB）是儿童最常见的恶性脑肿瘤。热休克蛋白（HSPs）是一类蛋白质超家族，作为分子伴侣发挥作用，在多种人类癌症中过表达。本研究的目的是通过对髓母细胞瘤进行多重微珠阵列分析，研究HSP27（pSer(82)）、HSP27（pSer(15)）、HSP40、HSP60、HSP70、HSP90-α、Akt和磷酸化Akt的表达情况。HSP和Akt表达结果与髓母细胞瘤亚型、Ki-67指数、bcl-2和p53的免疫组化表达以及患者预后相关。
作者回顾性评估了25例接受手术的儿童髓母细胞瘤患者。对所有病例进行了Ki-67、p53和bcl-2表达的免疫组化分析。通过多重微珠阵列分析，同时检测HSP27（pSer(82)）、HSP27（pSer(15)）、HSP40、HSP60、HSP70、HSP90-α、Akt和磷酸化Akt。
与经典型髓母细胞瘤相比，广泛结节型髓母细胞瘤的HSP27（pSer(15)）表达显著降低（p = 0.039），但HSP60表达显著升高（p = 0.021）。大细胞型髓母细胞瘤的HSP70表达显著高于经典型髓母细胞瘤（p = 0.028）。HSP27（pSer(82)）、HSP40、HSP90-α、Akt或磷酸化Akt表达与髓母细胞瘤亚型之间未发现显著差异。与经典型髓母细胞瘤相比，大细胞型髓母细胞瘤的Ki-67指数显著更高（p = 0.033）。分析所有髓母细胞瘤时，HSP27（pSer(15)）与Ki-67指数之间存在显著负相关（r = -0.475，p = 0.016）；HSP70表达与Ki-67指数之间存在显著正相关（r = 0.407，p = 0.043）；HSP70表达与bcl-2指数之间存在显著正相关（r = 0.491，p = 0.023）。大细胞型髓母细胞瘤患者的生存率低于经典型髓母细胞瘤患者，但差异未达到统计学意义（p = 0.076）。
观察到髓母细胞瘤中有几种HSPs的大量表达。鉴于HSPs是抗癌治疗的一个有吸引力的策略，显然需要进一步开展涉及更多患者的研究，以阐明HSPs与肿瘤侵袭性和预后的关系。
