胰腺癌组织中p16基因缺失及其对p16蛋白表达的影响

Deletion of p16 gene and its impact on the expression of p16 protein in pancreatic carcinoma

目的 探讨胰腺癌组织中p16基因缺失状态及其对p16蛋白表达的影响。方法 采用聚合酶链反应技术分别检测经显微切割方法获取的p16蛋白免疫组化染色阳性和阴性的胰腺癌组织中p16基因纯合性缺失状态并将结果与p16蛋白表达之间的关系进行分析。结果 32例胰腺癌中分别有20例（62．5％）和21例（65．6％）表现为p16蛋白表达丢失和p16基因纯合性缺失，其中有5例发生于p16基因的第1外显子，12例缺失发生于第2外显子，1例发生于第3外显子，另有3例同时发生于第1和第2外显子。此外还发现无p16蛋白表达的胰腺癌组织发生p16基因纯合性缺失的比例（18／20，90．0％）高于有p16蛋白表达的胰腺癌（3／12，25．0％）；在无p16蛋白表达并伴有p16基因缺失的7例胰腺癌病人中仅有1例生存期超过5mo，而二者均无异常的3例胰腺癌的生存期均超过8mo。结论 胰腺癌组织中的p16基因纯合性缺失可以影响p16蛋白的表达，促使胰腺癌病人的预后更差。

Objective The purpose of the study was to assess the status of homozygous deletion （HD） of p16 gene and its effect on the expression of p16 protein in primary pancreatic adenocarcinoma. Methods Polymerase chain reaction was used for detecting HD of p16 gene in pancreatic adenocarcinorna tissue obtained by microdissecting based on result of immunohistochemieal staining of p16 protein, and then to correlation between HD of p16 gene to the expression of p16 protein. Results 21 （65.6%） and 20 （62.5%） in 32 cases of pancreatic carcinoma showed HD of p16 gene and no expression of p16 protein, respectively. Among 21 cases of liD 12 cases are involved in exon 2, 5 in exon, 1 in exon 3, and 3 in exon 1 and exon 2 simultaneously. In addition, proportion of HD of p16 gene in pancreatic carcinomas without expression of p16 protein （18/20, 90.0%） was higher than in those with p16 protein expression （3/12, 25.0%）, and moreover, of seven patients with concomitant HD of p 16 gene and no expression of p 16 protein only one survived for more than 5 months, and but all three patients without these two alternations survived for more than 8 months. Conclusions These results suggest that HD of p16 gene may impact the expression of p16 protein in pancreatic cancer, and make patients with pancreatic cancer worse prognosis.