TP53 MUTATIONS AND ABNORMAL P53 PROTEIN STAINING IN BREAST CARCINOMAS RELATED TO PROGNOSIS
TP53 MUTATIONS AND ABNORMAL P53 PROTEIN STAINING IN BREAST CARCINOMAS RELATED TO PROGNOSIS
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DOI：
10.1016/0959-8049(95)00399-4
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发表时间：
1995-10-01
影响因子：
8.4
通讯作者：
EYFJORD, JE
中科院分区：
文献类型：
--
作者：
THORLACIUS, S;THORGILSSON, B;EYFJORD, JE
在106例乳腺癌中检测了TP53抑癌基因的缺失，并与临床结果进行了比较。采用免疫组化染色和聚合酶链反应-恒定变性凝胶电泳（PCR-CDGE）分析，然后进行PCR和直接测序，对肿瘤进行p53异常筛查。通过比较正常和肿瘤DNA，用多态性标记确定TP53位点的等位基因丢失。对于大约一半的患者，通过ELISA测定确定血清中的异常p53蛋白表达。37.6（38/101）例p53基因突变和/或核染色异常。33.7%的肿瘤细胞核可见p53蛋白染色。在18.9%的肿瘤中检测到外显子5 - 8的突变，并且发现突变与核染色之间存在关联。与没有突变的肿瘤（45.8%）相比，在TP53基因显示变化的肿瘤（72.7%）中17 p上TP53区域的等位基因丢失更频繁。血清p53抗体水平与TP53突变或核染色均无相关性。在研究期间，肿瘤中有TP53突变的女性死亡风险升高（RR（相对风险）= 3.4，P = 0.014）。p53阳性表达的影响相似（RR = 3.2，P = 0.013）。考虑到所有异常、突变和/或染色，死于乳腺癌的相对风险为3.5（P = 0.008）。
Abnormalities in the TP53 tumour suppressor gene were evaluated in 106 unselected breast carcinomas and compared to clinical outcome of the disease. Tumours were screened for p53 abnormalities using immunohistochemical staining and polymerase chain reaction-constant denaturant gel electrophoresis (PCR-CDGE) analysis, followed by PCR and direct sequencing. Allelic loss at the TP53 locus was determined with polymorphic markers by comparing normal and tumour DNA. For approximately half of the patients, abnormal p53 protein expression in serum was determined by an ELISA assay. p53 abnormalities, detected as mutations and/or nuclear staining, were found in 37.6 (38/101) of cases. Nuclear staining for p53 protein could be identified in 33.7% of the tumours. Mutations in exons 5-8 were detected in 18.9% of the tumours, and an association was found between mutations and nuclear staining. Allelic loss in the TP53 region on 17p was more frequent in tumours showing changes in the TP53 gene (72.7%) compared to tumours with no mutation (45.8%). Serum levels of p53 antibodies showed no association with either TP53 mutations or nuclear staining. Women with TP53 mutations in their tumours had an elevated risk of dying during the study period (RR (relative risk) = 3.4, P = 0.014). The effects of p53 positive staining were similar (RR = 3.2, P = 0.013). Considering all abnormalities, mutation and/or staining, the relative risk of dying from breast cancer was 3.5 (P = 0.008).