Expression of aberrant beta-catenin and impaired p63 in craniopharyngiomas
1Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Abstract:
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.
Insights
Craniopharyngiomas (CPs) show distinct molecular features. Adamantinomatous CPs exhibit aberrant beta-catenin, while both types display p63 overexpression, linked to altered p63 mRNA levels.
Area of Science:
- Oncology
- Pathology
- Molecular Biology
Background:
- Craniopharyngiomas (CPs) are rare sellar region tumors with unknown molecular pathogenesis.
- Understanding CPs' molecular drivers is crucial for diagnosis and treatment.
Purpose of the Study:
- To investigate aberrant beta-catenin and p63 expression in adamantinomatous (adaCPs) and squamous papillary (spCPs) craniopharyngiomas.
- To correlate p63 protein levels with mRNA expression in CPs.
Main Methods:
- Immunohistochemistry was used to assess beta-catenin and p63 expression in 66 CPs (51 adaCPs, 15 spCPs).
- Quantitative real-time PCR analyzed p63 mRNA isoforms (TAp63, DeltaNp63) in snap-frozen tissues.
Main Results:
- Aberrant nuclear/cytoplasmic beta-catenin was found exclusively in 47/51 adaCPs.
- P63 overexpression was observed in 45/51 adaCPs and 14/15 spCPs.
- CPs showed reduced TAp63 mRNA and elevated DeltaNp63 mRNA compared to normal tissues.
Conclusions:
- Beta-catenin accumulation is a hallmark of adaCPs.
- P63 is overexpressed in both CPs variants.
- Impaired p63 expression in CPs is associated with altered TAp63/DeltaNp63 mRNA ratios.
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