Sakatani S, Kusakabe H, Kiyokane K, Suzuki K
Department of Dermatology, Osaka Medical College, Takatsuki City, Japan.
Am J Dermatopathol. 1998 Oct;20(5):463-7. doi: 10.1097/00000372-199810000-00006.
We determined the relationship between p53 expression and p53 gene mutations in squamous cell carcinoma occurring in scars and unrelated to UV light irradiation. We analyzed biopsy specimens obtained from three patients with squamous cell carcinoma. A monoclonal antibody against p53 (DO-7) was used for the immunohistochemical analysis. p53 gene mutations were detected by the polymerase chain reaction and single-strand conformation polymorphism analysis and direct DNA sequencing. p53 overexpression was observed in atypical squamous cells of one case. Those of two other cases, however, showed negative immunoreactivity to p53. Exon 6 of the p53 gene in all three cases and exon 7 in one case showed electrophoretic mobility shifts in polymerase chain reaction and single-strand conformation polymorphism analysis. DNA sequencing analysis showed a missense mutation and a silent mutation in exon 6 of the case with p53 overexpression, a three-base deletion in exon 6 of one case with no p53 overexpression, and a three-base deletion in exon 6 and a missense mutation in exon 7 of another such case. Although immunohistochemical overexpression of p53 has been thought to result from p53 gene mutations, our results suggest that negative immunoreactivity to p53 also can result from p53 gene mutations, for example, short gene deletions.
我们确定了瘢痕中发生的、与紫外线照射无关的鳞状细胞癌中p53表达与p53基因突变之间的关系。我们分析了从三名鳞状细胞癌患者获取的活检标本。采用抗p53单克隆抗体（DO-7）进行免疫组织化学分析。通过聚合酶链反应、单链构象多态性分析及直接DNA测序检测p53基因突变。在1例患者的非典型鳞状细胞中观察到p53过表达。然而，其他2例患者对p53呈免疫反应阴性。在聚合酶链反应和单链构象多态性分析中，所有3例患者的p53基因第6外显子以及1例患者的第7外显子均出现电泳迁移率改变。DNA测序分析显示，p53过表达患者的第6外显子存在错义突变和沉默突变，1例无p53过表达患者的第6外显子有3个碱基缺失，另1例此类患者的第6外显子有3个碱基缺失且第7外显子有错义突变。尽管一直认为p53免疫组织化学过表达是由p53基因突变所致，但我们的结果表明，p53免疫反应阴性也可能由p53基因突变引起，比如短基因缺失。
