Lianidou E S, Levesque M A, Katsaros D, Angelopoulou K, Yu H, Genta F, Arisio R, Massobrio M, Bharaj B, Diamandis E P
Department of Chemistry, University of Athens, Greece.
Anticancer Res. 1999 Jan-Feb;19(1B):749-56.
p53 alteration, detected as mutation of the p53 gene or as accumulation of mutant p53 protein, is a common feature of most malignancies, including ovarian carcinoma, and may identify patients with unfavorable prognosis and resistance to chemotherapy. Tumor tissues from 55 patients with well or poorly differentiated (grades 1 or 3) primary epithelial ovarian carcinoma were assessed both for p53 protein overexpression by a sensitive time-resolved immunofluorometric assay employing DO-1 and CM-1 antibodies, and for genetic p53 abnormalities by direct sequencing of PCR-amplified exons 5 to 9. Sixteen p53 mutations (29%), including 3 deletions causing frameshifts as well as one nonsense and 12 missense point mutations were found in all exons except exon 9. Overexpression of p53 protein, defined as a concentration exceeding the 75th percentile, was found in 15 cases (27%), 10 of which had missense mutations (P < 0.01). Tumors with nonsense and frameshift mutations were p53-negative by immunoassay. Both p53 mutation (P = 0.04) and p53 protein accumulation (P < 0.01) were associated with stage III-IV disease, while p53 mutation was more closely related to grade 3 lesions (P = 0.04) and serous histotype (P = 0.01). These results indicate that p53 protein accumulation correlates well with missense point mutation in carcinoma of the ovary and, together with other evidence that p53 abnormality may be prognostic of outcome in this disease, suggest that the immunoassay of p53 protein may have clinical value.
p53改变，表现为p53基因突变或突变型p53蛋白的积累，是包括卵巢癌在内的大多数恶性肿瘤的常见特征，可能预示患者预后不良且对化疗耐药。采用DO-1和CM-1抗体，通过灵敏的时间分辨免疫荧光分析法评估了55例高分化或低分化（1级或3级）原发性上皮性卵巢癌患者肿瘤组织中的p53蛋白过表达情况，并通过对PCR扩增的外显子5至9进行直接测序来检测p53基因异常。除外显子9外，在所有外显子中均发现了16个p53突变（29%），包括3个导致移码的缺失突变、1个无义突变和12个错义点突变。p53蛋白过表达定义为浓度超过第75百分位数，在15例（27%）患者中发现，其中10例有错义突变（P<0.01）。无义突变和移码突变的肿瘤免疫检测p53呈阴性。p53突变（P=0.04）和p53蛋白积累（P<0.01）均与Ⅲ-Ⅳ期疾病相关，而p53突变与3级病变（P=0.04）和浆液性组织学类型（P=0.01）关系更为密切。这些结果表明，卵巢癌中p53蛋白积累与错义点突变密切相关，并且结合其他表明p53异常可能预示该疾病预后的证据，提示p53蛋白免疫检测可能具有临床价值。
