P~(16)、P~(53)、P~(21)/WAF1蛋白的表达与原发性肝癌诊断与预后关系的研究

目的:探讨肝癌和癌旁组织中P~(16)、P~(53)、P~(21)/WAF1蛋白的表达与原发性肝癌的诊断和预后的关系。方法:应用免疫组化技术检测48例手术切除肝癌及癌旁组织中肿瘤相关基因的表达。结果:P~(16)、P~(53)、P~(21)/WAF1蛋白在肿瘤组织中的阳性表达分别为39.6％、56.2％、43.7％,与癌旁组织中的表达差异有显著性(P<0.05),瘤体直径大于5cm、包膜不完整的肿瘤、生存期小于2年和伴有瘤栓的肿瘤组中,P~(21)、P(53)、P~(16)与癌旁组织的表达差异有显著性(P<0.05);在生存期大于2年和复发时间大于6个月的病例中,肿瘤组织表达P~(16)蛋白明显高于生存期小于2年和复发时间小于6个月的病例(P<0.05);在伴有瘤栓和侵润生长的肿瘤组织中P~(53)蛋白表达与不伴有瘤栓和膨胀生长的表达差异有显著性;P~(21)在低分化和早期复发的肿瘤组织中表达显著高于高分化和复发时间较晚的肿瘤组织(P<0.05)。结论:P~(53)基因突变与肝癌的分期、门静脉癌栓的形成、肿瘤的侵袭性有关,是肝癌发展的晚期事件,P~(21)与肝癌的分化和预后有关;P~(16)与肝癌的复发和预后有关。P~(16)、P~(53)、P~(21)可以作为对肝癌分化、侵袭、转移和预后进行预测的标志。

A study on expression of P16 P53 P21/WAF1 Proteim for the diagnoses and prognosis of hepatocellular carcinoma

Objective:To investigate the relationship between the expression of P16,P53,P21/WAF1 protein and the diagnoses or prognosis of hepatocelluljar carcinoma. Methods: Both postoperative tumor tissues and pericarcinomatous tiver tissues from 48 cases of hepatocellular carcinoma (HCC) were examined by immunohistochemical method. Results:Positive rate for the expression of P16,P53and P21/WAF1 protein was 39. 6%>56. 2%and 43. 7%respectively in tumors tissnes, which were much higher than in tissues adjacent to tumor, respectively(P<0. 05). The abnormal expression of P53,P21and P16protein increased significantly with increasing tumor size, tumor infiltrating to capsule, tumor thrombosis and survival time less than two years (P<0. 05). In the cases of survival less than two years and recurrent time no more than six months, positive rate for the expression of P16 increased significantly in tumor tissues (P<0. 05). In the patients with tumor thrombosis and infiltrative growth, the expression of P53 protein was higher than pa- tients without tumor thrombosis and infiltrative growth (P<0. 05). The expression of P21protein increased significantly in tumor tissue with poor differentiation and recurrence time less than two years (P<0. 05). Conclusions:Mutation of P53 gene closely was associated with tumor progression, portal tumor thrombosis and tumor invasion, was a late event of tumor progression. P21protein was related to differentiation and prognosis of HCC. P16protein associated with prognosis and recurrence of HCC. These suggested that P16, P53and P21 may be significant indicators of tumor differentiation or invasion or metastasis and prognosis.