Expression of aberrant β-catenin and impaired p63 in craniopharyngiomas

Expression of aberrant β-catenin and impaired p63 in craniopharyngiomas
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DOI:
10.3109/02688690903576237
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发表时间:
2010-06-01
影响因子:
1.1
通讯作者:
Huang, Z. S.
Huang, Z. S.
中科院分区:
医学4区
文献类型:
--
作者:
Cao, J.;Lin, J. P.;Huang, Z. S.

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颅咽管瘤是一种罕见的,组织学上良性的,非神经上皮上皮性肿瘤,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(包括51例造釉细胞瘤型颅咽管瘤和15例鳞状乳头状颅咽管瘤)中β-连环蛋白的异常表达和p63的受损。在免疫组化上,51例造釉细胞瘤型颅咽管瘤中的47例,而非鳞状乳头状颅咽管瘤,显示β-连环蛋白的强核/胞浆表达,主要在紧密粘附的螺旋状排列的上皮细胞中,ki-67几乎不存在,很少在栅栏状细胞中,ki-67主要存在。在51例造釉细胞瘤型颅咽管瘤和15例鳞状乳头状颅咽管瘤中,分别有45例和14例出现P63过表达。P63不仅表达于基底层细胞核,而且在造釉细胞型颅咽管瘤中呈螺旋状排列,在鳞状乳头状颅咽管瘤中呈均匀分布。采用定量真实的时间聚合酶链反应技术,以相关的p63蛋白表达与p63 mRNA水平,TAp 63亚型的mRNA减少,而在5个速冻组织样品与多个大的p63阳性细胞簇相比,正常组织中的Δ Np 63 mRNA水平升高。总之,本研究证实了CP的两个变体在遗传上既有区别又有共同的特征。这表明,细胞质/细胞核β-连环蛋白积累是adaCP的唯一特征性形态。在同一研究中,P63免疫组化表达在adaCPs和spCPs变异体中均被发现。总之,受损的p63表达可能归因于CP中Delta Np 63 mRNA的升高和TAp 63 mRNA的降低。
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, 47out 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 Delta Np63 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 Delta Np63 mRNA and reduced TAp63mRNA in CPs.