Baas I O, Mulder J W, Offerhaus G J, Vogelstein B, Hamilton S R
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196.
J Pathol. 1994 Jan;172(1):5-12. doi: 10.1002/path.1711720104.
Immunohistochemical detection of intranuclear p53 gene product may indicate mutation of the p53 suppressor gene on chromosome 17p. We used six commercially available antibodies for p53 immunohistochemistry on 19 archival colorectal neoplasms and compared the results with the mutation status of the p53 gene and 17p allelic deletion status. By Friedman's ranking analysis, use of mouse monoclonal antibody DO7 with Target Unmasking Fluid (TUF) for antigen retrieval was the most sensitive and specific procedure (P < 0.0001). Six of 7 cases with high expression (p53 Labeling Index > 30 per cent using a CAS 200 image analyser) had p53 mutation. Of seven tumours without expression (LI < 1 per cent), six had no mutation and one had a truncating mutation which prohibited nuclear localization of gene product. The low expression group (1 per cent < LI < 30 per cent, n = 5) consisted of three tumours without and two tumours with mutation. The sensitivity of high expression with the DO7-TUF method for p53 gene mutation was 67 per cent with specificity of 90 per cent, predictive value of a positive of 86 per cent, predictive value of a negative of 75 per cent, and efficiency of 79 per cent. This study suggests that immunohistochemistry is valuable for assessing p53 gene mutations in colorectal neoplasms, but further study is needed to elucidate the precise link between immunohistochemistry and molecular genetic alterations.
细胞核内p53基因产物的免疫组织化学检测可能提示17号染色体短臂上p53抑癌基因的突变。我们使用六种市售的p53免疫组织化学抗体,对19例存档的结直肠肿瘤进行检测,并将结果与p53基因的突变状态和17号染色体短臂等位基因缺失状态进行比较。通过弗里德曼等级分析,使用小鼠单克隆抗体DO7和目标抗原修复液(TUF)进行抗原修复是最敏感和特异的方法(P<0.0001)。在7例高表达病例(使用CAS 200图像分析仪,p53标记指数>30%)中,有6例存在p53突变。在7例无表达的肿瘤(标记指数<1%)中,6例无突变,1例存在截短突变,该突变阻止了基因产物的核定位。低表达组(1%<标记指数<30%,n=5)包括3例无突变和2例有突变的肿瘤。DO7-TUF法检测p53基因突变的高表达敏感性为67%,特异性为90%,阳性预测值为86%,阴性预测值为75%,效率为79%。本研究提示,免疫组织化学对评估结直肠肿瘤中的p53基因突变有价值,但需要进一步研究以阐明免疫组织化学与分子遗传学改变之间的确切联系。