Angelopoulou K, Rosen B, Stratis M, Yu H, Solomou M, Diamandis E P
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
Cancer. 1996 Nov 15;78(10):2146-52.
Genetic alterations of the p53 tumor suppressor protein are the most frequent molecular events in human carcinogenesis. For as yet unknown reasons, mutant p53 often acts as an immunogen for autoantibody generation. These autoantibodies can be detected in the serum of cancer patients. The presence of such antibodies has been identified in a subset of patients with ovarian carcinoma, but their clinical significance has not been investigated.
Serum samples from patients with ovarian carcinoma were quantitatively analyzed for the presence of p53 autoantibodies with a time-resolved immunofluorometric procedure. Tumor p53 overexpression was assessed by immunohistochemical analysis of tissue sections. Kaplan-Meier survival curves were calculated for p53 antibody positive and negative patients, and the Cox model was used to evaluate the strength of the associations between the presence of serum p53 antibodies and cancer relapse or death, and also between the presence of such antibodies and other clinicopathologic features.
p53 antibodies were detected in the serum of 41 of 174 patients with ovarian carcinoma (24%). Antibody levels ranged from a few hundred to 9 x 10(6) arbitrary Units/L, and fluctuated during the course of the disease. p53 antibody positive patients tended to have tumors overexpressing p53, but the association between the two parameters was not statistically significant (P = 0.13). There was also no association between the presence of p53 antibodies and clinical stage, tumor histologic type, or overall patient survival. However, these antibodies were more frequently present in patients older than 50 years (P = 0.001), in patients with moderately or poorly differentiated tumors (P = 0.001), and in patients who received chemotherapy (P = 0.015), and who suffered relapse after surgery (P = 0.018). In univariate analysis, p53 antibody positive patients were at an increased risk for relapse but not death. In multivariate analysis, the differences in disease free and overall survival between patients who were p53 antibody positive or negative were not statistically significant.
p53 autoantibodies are found frequently in the serum of patients with ovarian carcinoma. The presence of such autoantibodies was associated with older patient age, more aggressive tumors, and reduced patient disease free survival. In multivariate analysis the prognostic value of p53 autoantibodies was not statistically significant.
p53肿瘤抑制蛋白的基因改变是人类致癌过程中最常见的分子事件。由于尚不清楚的原因，突变型p53常常作为自身抗体产生的免疫原。这些自身抗体可在癌症患者血清中检测到。在一部分卵巢癌患者血清中已发现此类抗体，但尚未对其临床意义进行研究。
采用时间分辨免疫荧光分析法对卵巢癌患者血清样本进行定量分析，以检测p53自身抗体的存在。通过对组织切片进行免疫组织化学分析评估肿瘤p53的过表达情况。计算p53抗体阳性和阴性患者的Kaplan-Meier生存曲线，并使用Cox模型评估血清p53抗体的存在与癌症复发或死亡之间的关联强度，以及此类抗体的存在与其他临床病理特征之间的关联强度。
174例卵巢癌患者中有41例（24%）血清中检测到p53抗体。抗体水平范围从几百到9×10⁶任意单位/升，且在疾病过程中波动。p53抗体阳性患者的肿瘤往往有p53过表达，但这两个参数之间的关联无统计学意义（P = 0.13）。p53抗体的存在与临床分期、肿瘤组织学类型或患者总体生存率之间也无关联。然而，这些抗体在年龄大于50岁的患者（P = 0.001）、肿瘤为中分化或低分化的患者（P = 0.001）、接受化疗的患者（P = 0.015）以及术后复发的患者（P = 0.018）中更常见。在单因素分析中，p53抗体阳性患者复发风险增加，但死亡风险未增加。在多因素分析中，p53抗体阳性或阴性患者的无病生存期和总生存期差异无统计学意义。
p53自身抗体在卵巢癌患者血清中频繁出现。此类自身抗体的存在与患者年龄较大、肿瘤侵袭性更强以及患者无病生存期缩短有关。在多因素分析中，p53自身抗体的预后价值无统计学意义。
