目的　深入研究p5 3蛋白空间结构的改变在甲状腺乳头状癌 (PTC)中的临床病理意义 ,为PTC的恶性度评价提供客观的指标。方法　采用PCR SSCP、DNA序列分析、以及利用国际共享资源计算机重构p5 3蛋白三维空间结构和有关分析软件等技术对 4 1例PTC进行分析。结果　p5 3基因突变Ⅰ组 (15例 )和未突变Ⅱ组 (2 6例 )的年龄、性别、原发瘤大小 (T)、淋巴结转移率 (N)和远处转移率 (M)无明显差异 (P >0 0 5 )。 9例 (9/ 15 ,Ⅰb组 )的氨基酸残基突变表现为核心功能域和碱性域的变化或核心功能域严重缺损。p5 3蛋白核心功能域结构的改变能直接抑制它与靶DNA的结合 ;碱性域结构的改变能间接抑制p5 3蛋白与靶DNA的结合。 6例 (6 / 15 ,Ⅰa组 )的氨基酸残基突变位于功能域之外。Ⅰb组的淋巴结转移率 (77 78% )明显高于Ⅰa组 (P <0 0 1) ,Ⅰb组的远处转移率(5 5 5 6 % )高于Ⅰa组 (P <0 0 5 )。结论　p5 3蛋白三维空间结构的改变是PTC演进与异质化的形态学基础之一 ,它可为选择高危PTC临床病例提供确凿的证据 Objective To study the clinicopathological significance of p35 protein spatial structure change in papillary thyroid carcinoma (PTC) and to provide an objective index for evaluating the malignancy of PTC. METHODS: PCR-SSCP and DNA sequence analysis were used to analyze 41 patients with PTC using the internationally shared resource computer to reconstruct the 3D spatial structure of p5 3 protein and related software. Results There were no significant differences in age, sex, size of primary tumor (T), lymph node metastasis (N) and distant metastasis (M) between group Ⅰ (15 cases) and group Ⅱ (26 cases) Difference (P> 0.05). Nine patients (9/15, Ⅰ b group) mutations in the amino acid residues showed changes in the core domains and basic domains or serious defects in the core domain. The change of the structure of p5 3 protein core domain can directly inhibit its binding with target DNA. The change of basic domain structure can indirectly inhibit the binding of p5 3 protein to target DNA. The amino acid residues in 6 cases (6/15, Ⅰa group) were located outside the functional domain. The rate of lymph node metastasis in group Ⅰb was significantly higher than that in group Ⅰa (77 78%) (P <0 01). The rate of distant metastasis in group Ⅰb (55 65%) was higher than that of group Ⅰa (77 0%). Conclusion The change of the three-dimensional structure of p5 3 protein is one of the morphological bases of PTC evolution and heterogeneity, which can provide conclusive evidence for the selection of high-risk PTC clinical cases