Umekita Y, Kobayashi K, Saheki T, Yoshida H
Department of Pathology, Faculty of Medicine, Kagoshima University.
Jpn J Cancer Res. 1994 Aug;85(8):825-30. doi: 10.1111/j.1349-7006.1994.tb02954.x.
Fifty invasive ductal carcinomas of the breast were analyzed by immunohistochemistry, polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and direct sequencing after microdissection of conventional formalin-fixed, paraffin-embedded tissues. A highly significant association between the presence of p53 gene mutation and nuclear accumulation of p53 protein was found (P < 0.0001). Of 13 tumors that demonstrated p53 gene mutations, 11 (84.6%) showed nuclear accumulation of p53 protein. However, of 37 tumors in which gene mutations were not detected, only 5 (13.5%) showed nuclear accumulation of p53 protein. There was a statistically significant association between the nuclear accumulation of p53 protein and a higher histological grade (P < 0.001) or mitotic index (P < 0.01). In addition, gene mutations had a statistically significant association with a higher histological grade (P < 0.05) or mitotic index (P < 0.0001). Therefore, p53 abnormalities might be associated with an aggressive phenotype in breast cancer. We conclude that the immunohistochemical detection of nuclear p53 protein accumulation is highly associated with p53 gene mutations in archival paraffin-embedded tissues, and that this method is useful for rapid screening of p53 abnormalities.
采用免疫组织化学、聚合酶链反应-单链构象多态性（PCR-SSCP）以及对常规福尔马林固定、石蜡包埋组织进行显微切割后的直接测序方法，对50例乳腺浸润性导管癌进行了分析。发现p53基因突变的存在与p53蛋白的核内积聚之间存在高度显著的相关性（P < 0.0001）。在13例显示p53基因突变的肿瘤中，11例（84.6%）表现出p53蛋白的核内积聚。然而，在37例未检测到基因突变的肿瘤中，只有5例（13.5%）表现出p53蛋白的核内积聚。p53蛋白的核内积聚与较高的组织学分级（P < 0.001）或有丝分裂指数（P < 0.01）之间存在统计学上的显著相关性。此外，基因突变与较高的组织学分级（P < 0.05）或有丝分裂指数（P < 0.0001）之间存在统计学上的显著相关性。因此，p53异常可能与乳腺癌的侵袭性表型有关。我们得出结论，存档石蜡包埋组织中核p53蛋白积聚的免疫组织化学检测与p53基因突变高度相关，并且该方法对于快速筛查p53异常是有用的。
