PROGNOSTIC-SIGNIFICANCE OF P53 OVEREXPRESSION IN PRIMARY BREAST-CANCER - A NOVEL LUMINOMETRIC IMMUNOASSAY APPLICABLE ON STEROID-RECEPTOR CYTOSOLS
PROGNOSTIC-SIGNIFICANCE OF P53 OVEREXPRESSION IN PRIMARY BREAST-CANCER - A NOVEL LUMINOMETRIC IMMUNOASSAY APPLICABLE ON STEROID-RECEPTOR CYTOSOLS
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DOI：
10.1038/bjc.1995.195
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发表时间：
1995-05-01
影响因子：
8.8
通讯作者：
BRUNDELL, J
中科院分区：
文献类型：
--
作者：
BORG, A;LENNERSTRAND, J;BRUNDELL, J
一种新型定量发光免疫分析 (LIA) 已被开发出来，用于测量乳腺肿瘤组织提取物中的野生型和突变型 p53 蛋白。与免疫组织化学分析获得的结果相比，LIA 可以对常规制备用于类固醇受体分析的胞质样品中的 p53 表达进行可靠的估计。对 205 个原发性乳腺肿瘤细胞质进行了 LIA 评估，这些细胞质为类固醇受体分析而准备，并在 -80 摄氏度下冷冻保存 6-8 年，在 65% 的样品中检测到 p53 蛋白（范围为 0.01-23 ng mg(-1) 蛋白）。使用0.15 ng mg(-1)蛋白的任意截止值，30%的肿瘤被分类为表现出p53过度表达。在中位随访时间为 50 个月时，发现 p53 过表达与较短的无病生存期 (P < 0.001) 和总生存期 (P = 0.039) 之间存在显着且独立的相关性。 p53 过度表达与低雌激素受体含量和高增殖率（S 期分数）有关。未发现与肿瘤大小或淋巴结转移的存在相关。三个肿瘤具有极高的p53含量（> 10 ng mg(-1)蛋白），均为髓质或高级导管型，雌激素和孕激素受体阴性，DNA非二倍体，S期分数> 22%，并在1-2年内复发。总之，我们开发了一种新的灵敏定量 LIA，适用于对乳腺肿瘤类固醇受体胞质制剂中的 p53 蛋白进行常规分析，以证实 p53 蛋白积累在人类乳腺癌中的预后重要性。
A novel quantitative luminometric immunoassay (LIA) has been developed for the measurement of wild-type and mutant p53 protein in extracts from breast tumour tissue. The LIA was found to yield reliable estimates of p53 expression in cytosol samples routinely prepared for steroid receptor analysis as compared with results obtained with immunohistochemical analysis. The LIA was evaluated on 205 primary breast tumour cytosols prepared for steroid receptor analysis and stored frozen at -80 degrees C for 6-8 years, p53 protein being detected in 65% of the samples (range 0.01-23 ng mg(-1) protein). Using an arbitrary cut-off value of 0.15 ng mg(-1) protein, 30% of the tumours were classified as manifesting p53 overexpression. Significant and independent correlations were found to exist between p53 overexpression and shorter disease-free (P < 0.001) and overall survival (P = 0.039) at a median duration of follow-up of 50 months. p53 overexpression was related to low oestrogen receptor content and high proliferation rate (S-phase fraction). No relationship was found to tumour size or the presence of lymph node metastasis. Three tumours possessed an extremely high p53 content (> 10 ng mg(-1) protein), all of which were of medullary or high-grade ductal type, oestrogen and progesterone receptor negative, DNA non-diploid, had S-phase fractions of > 22% and recurred within 1-2 years. In summary, a new sensitive and quantitative LIA suitable for routine analysis of p53 protein in steroid receptor cytosol preparations from breast tumours has been developed to confirm the prognostic importance of p53 protein accumulation in human breast cancer.