Raedle J, Oremek G, Welker M, Roth W K, Caspary W F, Zeuzem S
Second Department of Internal Medicine, Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.
Pancreas. 1996 Oct;13(3):241-6. doi: 10.1097/00006676-199610000-00005.
In human pancreatic carcinoma (PCa) mutations in the p53 tumor suppressor gene are present in up to 50% of cases. Conformational change and cellular accumulation, together with subsequent release of mutant and normal p53 protein from transformed cells, may initiate a B-cell response with generation of circulating autoantibodies to p53 protein (anti-p53). In the present study we analyzed the sera of 85 consecutive patients with acute pancreatitis (N = 19), chronic pancreatitis (N = 33), and PCa (N = 33) to evaluate the specificity of autoantibodies to p53 protein as a serological marker for PCa. Detection of anti-p53 was performed using an enzyme-linked immunosorbent assay system with immobilized recombinant wild-type p53 protein. Autoantibodies to p53 were detectable in 1 of 19 patients with acute (5.3%) and in 4 of 33 patients with chronic pancreatitis (12.1%). All anti-p53-positive patients with acute or chronic pancreatitis were carefully examined and no underlying malignant disease was found. During follow-up (range, 281-647 days; mean, 472 days) none of these patients showed any evidence for subsequent development of PCa or any other malignant disease. In patients with PCa, anti-p53 was detected in 6 of 33 cases, resulting in a sensitivity of 18.2% with a specificity of 90.4%. In contrast to anti-p53, detection of serum carbohydrate antigen (CA 19-9) resulted in a sensitivity and specificity of 69.7 and 71.2% (CA 19-9, > 37 U/ml) and 51.5 and 96.2% (CA 19.9, > 100 U/ml) for the detection of PCa, respectively. Taken together, the sensitivity of anti-p53 formation was low in patients with PCa (18.2%). Furthermore, the detection of anti-p53 was not specific for malignancy, indicating that severe inflammatory processes may also induce anti-p53 formation.
在人类胰腺癌（PCa）中，p53肿瘤抑制基因的突变在高达50%的病例中存在。构象改变和细胞内蓄积，以及随后从转化细胞中释放突变型和正常p53蛋白，可能引发B细胞反应，产生针对p53蛋白的循环自身抗体（抗p53）。在本研究中，我们分析了85例连续的急性胰腺炎患者（n = 19）、慢性胰腺炎患者（n = 33）和PCa患者（n = 33）的血清，以评估针对p53蛋白的自身抗体作为PCa血清学标志物的特异性。使用固定化重组野生型p53蛋白的酶联免疫吸附测定系统检测抗p53。19例急性胰腺炎患者中有1例（5.3%）和33例慢性胰腺炎患者中有4例（12.1%）可检测到针对p53的自身抗体。所有抗p53阳性的急性或慢性胰腺炎患者均经过仔细检查，未发现潜在的恶性疾病。在随访期间（范围为281 - 647天；平均472天），这些患者中没有任何一人显示出随后发生PCa或任何其他恶性疾病的迹象。在PCa患者中，33例中有6例检测到抗p53，敏感性为18.2%，特异性为90.4%。与抗p53相反，血清糖类抗原（CA 19 - 9）检测对于PCa检测的敏感性和特异性分别为69.7%和71.2%（CA 19 - 9，> 37 U/ml）以及51.5%和96.2%（CA 19.9，> 100 U/ml）。综上所述，PCa患者中抗p53形成的敏感性较低（18.2%）。此外，抗p53的检测对恶性肿瘤不具有特异性，表明严重的炎症过程也可能诱导抗p53的形成。
