Cao J, Lin J P, Yang L X, Chen K, Huang Z S
Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Br J Neurosurg. 2010 Jun;24(3):249-56. doi: 10.3109/02688690903576237.
Craniopharyngiomas are rare, histologically benign, non-neuroepithelial epithelial tumors arising from the sellar region, the molecular pathogenesis of CPs is yet not understood. The aim of the present study was to assess expression of aberrant beta-catenin and impaired p63 in 66 craniopharyngiomas included 51 adamantinomatous craniopharyngiomas and 15 squamous papillary craniopharyngiomas. On immunohistochemistry, 47 out of 51 adamantinomatous craniopharyngiomas, but not squamous papillary craniopharyngiomas, showed strong nuclear/cytoplasmic expression for beta-catenin predominantly in compactly cohesive epithelial cells within the whorl-like arrays where ki-67 was almost absent and rarely in palisaded cells where ki-67 was mainly present. P63 overexpression was observed in 45 out of 51 adamantinomatous craniopharyngiomas and 14 out of 15 squamous papillary craniopharyngiomas. P63 stained not only in the nuclei of basal layer cells but also within the whorl-like arrays in adamantinomatous craniopharyngiomas and uniformly in squamous papillary craniopharyngiomas. Using quantitative real time polymerase chain reaction techniques to correlate p63 protein expression with p63 mRNA levels, TAp63 isoforms mRNA was reduced, whereas DeltaNp63 mRNA elevated at levels in 5 snap frozen tissue samples with multiple large p63 positive cell clusters compared with normal tissues. In conclusion, the present study confirmed that the two variants of CPs have genetically not only distinctive but also common feature. It demonstrated that cytoplasm/nuclear beta-catenin accumulation is an exclusively characteristic morphology of adaCPs. P63 immunohistochemical overexpression were found in both adaCPs and spCPs variant when analyzed in the same study. Taken together, the impaired p63 expression may be attributed to elevated DeltaNp63 mRNA and reduced TAp63mRNA in CPs.
颅咽管瘤是一种罕见的、组织学上良性的非神经上皮性上皮肿瘤,起源于鞍区,其分子发病机制尚不清楚。本研究的目的是评估66例颅咽管瘤中异常β-连环蛋白的表达和p63的缺失情况,其中包括51例造釉型颅咽管瘤和15例鳞状乳头型颅咽管瘤。免疫组化显示,51例造釉型颅咽管瘤中有47例(鳞状乳头型颅咽管瘤未出现此情况)β-连环蛋白在细胞核/细胞质中呈强表达,主要位于漩涡状排列的紧密聚集上皮细胞中,此处几乎没有Ki-67表达,而在主要存在Ki-67的栅栏状细胞中很少见。51例造釉型颅咽管瘤中有45例、15例鳞状乳头型颅咽管瘤中有14例观察到p63过表达。在造釉型颅咽管瘤中,p63不仅在基底层细胞核中染色,也在漩涡状排列中染色,而在鳞状乳头型颅咽管瘤中则均匀染色。使用定量实时聚合酶链反应技术将p63蛋白表达与p63 mRNA水平相关联,与正常组织相比,在5个有多灶大p63阳性细胞簇的冰冻组织样本中,TAp63亚型mRNA水平降低,而DeltaNp63 mRNA水平升高。总之,本研究证实颅咽管瘤的两种变体在遗传上不仅具有独特特征,也有共同特征。结果表明,细胞质/细胞核β-连环蛋白积累是造釉型颅咽管瘤独有的特征形态。在同一研究中分析发现,造釉型颅咽管瘤和鳞状乳头型颅咽管瘤变体中均存在p63免疫组化过表达。综上所述,颅咽管瘤中p63表达受损可能归因于DeltaNp63 mRNA水平升高和TAp63 mRNA水平降低。