Clinicopathologic significance of structural alterations of p53 protein in papillary thyroid carcinoma / 中华病理学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To make a thorough study on the clinicopathologic significance of the three-dimensional structural alteration of the p53 protein in papillary thyroid carcinomas and to provide an objective criterion for the evaluation of PTC prognosis.</p><p><b>METHODS</b>A total of 41 PTC cases were enrolled. Techniques including polymerase chain reaction with single strand conformational polymorphism (PCR-SSCP), DNA sequencing, computerized three-dimensional protein modeling by means of international shared resources and related software analysis were used.</p><p><b>RESULTS</b>15 cases with p53 gene mutation defined as Group I were detected in totally 41 PTC cases. No p53 gene mutation was found in the rest 26 cases which were classified as Group II. The differences in lymph node metastatic rate, distant metastatic rate, age, sex, size of the lesion between Group I and Group II were not significant (P > 0.05). The alterations of the amino acid residues of 9 PTC cases out of the 15 p53-gene mutated patients (Group I) were either located in the p53-protein domains, mainly the core domain and the non-specific DNA binding basic domain, or the severely defect cases with the formation of widely divergent structures. It was found that the alterations of the structure of the core domain could directly check the binding of p53 protein to its target DNA molecules. In addition, the alterations of the structure of the basic domain could indirectly prohibit the binding. The ones mentioned above were classified as Group Ib. The rest of six cases with their p53 protein amino acid residues mutated beyond the domains were grouped as Group Ia. The differences in lymph node metastatic rate, distant metastatic rate between Group Ib and Group Ia were statistically significant (P < 0.01, P < 0.05) respectively.</p><p><b>CONCLUSIONS</b>The alterations of the three-dimensional structure of p53-protein is considered as one of the morphological basis of the progression and heterogeneity of PTC. They render an authentic evidence for the selection of the clinical cases with a poor risk for metastasis.</p>