p53功能在肝癌中表达的意义

Value of p53 functional expression in hepatocellular carcinoma

目的：为探讨p53功能及某些生物学行为在肝癌中表达的意义。方法：收集1997年1月至1998年12月52例原发性肝癌的临床资料，并对这52例手术切除的肝癌标本，分别用Westernblot结合DNA损伤剂诱导的方法检测野生型p53的功能，免疫组化检测p53蛋白的表达，PCR／SSCP方法检测p53基因在第5～8外显子的丢失情况及免疫组化检测肿瘤增殖细胞核抗原（PCNA）指数。结果：52例标本中，对例（59．6％）野生型P53丢失功能，31例（59．6％）p53蛋白表达阳性，27例（51．9％）p53基因在第5～8外显子有丢失。野生型p53的功能与p53蛋白的表达呈正相关，野生型p53的功能与p53基因突变呈正相关。PCNA高指数30例（57.7％）。在野生型p53功能丢失的31例中，26例（83．9％）P53蛋白表达阳性；24例（77．4％）P53基因在第5～8外显子的丢失，PCNA高指数24例（77.4％）。野生型p53功能丢失多表现在肝硬化的病例中（P＝0．0015）。结论：本组原发性肝癌中，59．6％有丢失野生型p53功能，常发生在合并肝硬化的病例中；PCNA高指数，p53蛋白表达阳性，p53基因的突变也常出现在p53功能丢失的病例中（P＜0．01）。当野生型p53功能丢失，肿瘤容易出现肝内转移、门脉癌栓和肿瘤生长比较快。

Objective: To observe the p53 function, some of pathological and molecular behaviors of hepatocellular carcinoma (HCC). Methods: The function of wild-type P53 was tested using Western blot analysis and DNA damge agent in ducing test for 52 specimens of HCC from January 1997 to December 1998. These 52 specimens were also examined immunohistochemically us ing anti -p5 3 and anti- PCNA monoclonal antibodies. For mutations of p53 alterations in exons 5 ~8 of the gene were determined using the single-stranded conformational polymorphism analysis of polymerase chain reaction products (PCR/SSCP) method. Results: Loss of wild-type p53 function was found in 31 cases (59. 6% ) of these 52 specimens. There were 31 cases (59. 6% ) with p53 protein positive expression and 27 cases (51. 9% ) with p53 mutation. p53 function had parallel correlation to p53 protein expression (r = 0. 6006, P =0. 00001) and to p53 gene mutation (r = o. 5879, P = o. o()Ool ). PCNA high index appeared in 3o cases (57. 7% ). ln the 3l sPecimens which loss of p53 function, 26 cases showed also p53 protein positive expression(83. 9% ), p53 gene mutation in 24 cases (77. 4% ),PCNA high index in 24 cases (77. 4% ). This data showed that p53 function had close relationship with the liver cirrhosis.Loss wild-type p53 function usually appeared in the HCC with liver cirrhosis (P = 0. 0015 ). Conclusion: High index of PCNA, positive expression of p53 protein, p53 gene mutation frequently appeared in the cases with loss of wild-type p53 function (all of the P < 0. 01 ). Also when the tumor appeared loss of wild- type p53 function, the tumor showed early intrahepatic metastasis, porial vein embolus and growth more rapidly.