El-Habr E A, Tsiorva P, Theodorou M, Levidou G, Korkolopoulou P, Vretakos G, Petraki L, Michalopoulos N V, Patsouris E, Saetta A A
Department of Pathology, National and Kapodistrian University of Athens, Athens, Greece.
Clin Neuropathol. 2010 Jul-Aug;29(4):239-45. doi: 10.5414/npp29239.
The analysis of the presence of PIK3CA and B-RAF gene mutations in relation to ERK and AKT activation in diffusely infiltrating astrocytomas, in order to determine their potential role in tumor aggressiveness.
Polymerase chain reaction-single strand confirmation polymorphism (PCR-SSCP) and sequencing analysis were used for PIK3CA and B-RAF gene mutation detection. pERK and pAKT expression were examined by immunohistochemistry.
PIK3CA mutations were found in 2 (3%) cases of glioblastomas whereas none of these cases displayed mutations in exon 15 of B-RAF gene. Neither low grade astrocytomas nor anaplastic astrocytomas revealed any mutations in these genes. Nuclear and cytoplasmic pERK immunoreactivity was displayed in 100% and 82% of cases, respectively. pERK nuclear expression was positively correlated with pERK cytoplasmic expression (p = 0.0067). Moreover, pERK nuclear expression increased in parallel with tumor grade (II, III v/s IV, p = 0.0262). Nuclear and cytoplasmic pAKT immunoreactivity was displayed in 97% and 100% of cases, respectively. Similarly, pAKT nuclear expression was positively correlated with pAKT cytoplasmic expression (p = 0.0074). pAKT cytoplasmic expression increased with increasing tumor grade (II,III v/s IV, p = 0.0930), although the latter relationship was of marginal significance. pAKT cytoplasmic expression was also positively correlated with pERK nuclear expression (p = 0.0156).
Our study reports the low frequency of PIK3CA and B-RAF mutations in astrocytomas, despite the presence of activated ERK and AKT proteins. Moreover, the correlation of pERK nuclear and pAKT cytoplasmic expression with tumor grade suggests the possible crucial role of the activation of these proteins in human gliomagenesis.
分析弥漫性浸润性星形细胞瘤中PIK3CA和B-RAF基因突变的存在情况及其与ERK和AKT激活的关系，以确定它们在肿瘤侵袭性中的潜在作用。
采用聚合酶链反应-单链构象多态性（PCR-SSCP）和测序分析检测PIK3CA和B-RAF基因突变。通过免疫组织化学检测pERK和pAKT表达。
在2例（3%）胶质母细胞瘤中发现PIK3CA突变，而这些病例中均未显示B-RAF基因第15外显子突变。低级别星形细胞瘤和间变性星形细胞瘤均未发现这些基因的任何突变。100%的病例显示核pERK免疫反应性，82%的病例显示胞质pERK免疫反应性。pERK核表达与pERK胞质表达呈正相关（p = 0.0067）。此外，pERK核表达随肿瘤分级增加而升高（II、III级与IV级相比，p = 0.0262）。97%的病例显示核pAKT免疫反应性，100%的病例显示胞质pAKT免疫反应性。同样，pAKT核表达与pAKT胞质表达呈正相关（p = 0.0074）。pAKT胞质表达随肿瘤分级增加而升高（II、III级与IV级相比，p = 0.0930），尽管后者的关系具有边缘显著性。pAKT胞质表达也与pERK核表达呈正相关（p = 0.0156）。
我们的研究报告了星形细胞瘤中PIK3CA和B-RAF突变的低频率，尽管存在激活的ERK和AKT蛋白。此外，pERK核表达和pAKT胞质表达与肿瘤分级的相关性表明这些蛋白的激活在人类胶质瘤发生中可能起关键作用。
