Ralhan R, Nath N, Agarwal S, Mathur M, Wasylyk B, Shukla N K
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi.
Clin Cancer Res. 1998 Sep;4(9):2147-52.
p53 aberrations are early events in the pathogenesis of betel- and tobacco-related oral malignancies. Accumulation of p53 protein in oral lesions may elicit a humoral immune response against p53 protein in these patients. p53 antibodies (Abs) were analyzed in 183 sera obtained from patients with premalignant or malignant oral lesions and normal individuals by enzyme-linked immunoassay using recombinant p53 protein as antigen. These results were correlated with accumulation of p53 protein in patients' matched oral tissue specimens. Circulating p53 Abs were observed in 24 of 70 (34%) cancer patients and 15 of 50 (30%) patients with premalignant oral lesions. p53 Abs showed a significant association with increase in tumor size and dedifferentiation of tumors, factors indicative of poor prognosis. Expression of p53 protein was analyzed in 43 matched oral lesions (18 premalignant and 25 malignant cases). All the p53-seropositive patients (7 leukoplakia and 11 squamous cell carcinoma) showed elevated levels of p53 protein in matched oral lesions. However, the total number of patients seropositive for p53 Abs was lesser than that of patients exhibiting p53 protein accumulation in oral lesions. Four of the 63 normal healthy individuals who were heavy consumers of tobacco (smoking/chewing) and betel were found to be positive for p53 Abs. Detection of circulating p53 Abs in patients with premalignant oral lesions suggests that humoral immune response against p53 protein is an early event in oral oncogenesis and may be a surrogate marker for both p53 alteration and preclinical cancer.
p53畸变是槟榔和烟草相关口腔恶性肿瘤发病机制中的早期事件。口腔病变中p53蛋白的积累可能会引发这些患者针对p53蛋白的体液免疫反应。通过使用重组p53蛋白作为抗原的酶联免疫吸附测定法，对183份来自口腔癌前或恶性病变患者及正常个体的血清进行了p53抗体（Abs）分析。这些结果与患者匹配的口腔组织标本中p53蛋白的积累情况相关。在70例癌症患者中有24例（34%）以及50例口腔癌前病变患者中有15例（30%）检测到循环p53 Abs。p53 Abs与肿瘤大小增加和肿瘤去分化显著相关，这些因素表明预后不良。对43例匹配的口腔病变（18例癌前病变和25例恶性病变）进行了p53蛋白表达分析。所有p53血清阳性患者（7例白斑和11例鳞状细胞癌）在匹配的口腔病变中均显示p53蛋白水平升高。然而，p53 Abs血清阳性患者的总数少于口腔病变中出现p53蛋白积累的患者。在63名大量吸烟/咀嚼烟草和槟榔的正常健康个体中，有4例p53 Abs呈阳性。在口腔癌前病变患者中检测到循环p53 Abs表明，针对p53蛋白的体液免疫反应是口腔肿瘤发生的早期事件，可能是p53改变和临床前癌症的替代标志物。
