Molecular and immunohistochemical analysis of p53 mutations in scrapings and tissue from preinvasive and invasive breast cancer
Molecular and immunohistochemical analysis of p53 mutations in scrapings and tissue from preinvasive and invasive breast cancer
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DOI：
10.1007/s004280050114
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发表时间：
1997-12-01
期刊：
影响因子：
--
通讯作者：
Löning, T
中科院分区：
文献类型：
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作者：
Lisboa, BW;Vogtländer, S;Löning, T
p53基因突变似乎是人类癌症中最常见的异常之一。虽然已经发表了许多关于乳腺癌中p53突变的研究，但原位病变中p53突变的分子生物学检测数据仍然很少，并且对乳腺癌发生的影响尚不清楚。采用聚合酶链反应（PCR）和温度梯度凝胶电泳（TGGE）对83例不同分期的乳腺癌患者和13例乳腺良性病变患者的组织样本进行p53基因突变筛查。通过免疫组织化学（IHC）分析p53蛋白积聚。从新鲜冷冻组织、刮片中获得样品。或石蜡包埋组织。此外，还检查了23对原发性肿瘤和相应的淋巴结。p53基因在浸润癌、导管原位癌和导管不典型增生中的检出率分别为55.7%、31.5%和1例。与高级别肿瘤和粉刺呈正相关。与年龄、绝经状态、肿瘤大小、激素受体状态或淋巴浸润无统计学显著关系。TGGE和IHC之间的一致性仅见于63%的分析病例。然而，对于p53突变筛查TGGE，一个高的意义（P = 0.0008）之间看到标准组织提取和我们的刮制备技术。在8对原发性肿瘤及其相应的淋巴结转移灶中，只有3对在同一外显子上存在相同的p53突变，而在5例原发性肿瘤中存在突变p53的病例中，淋巴结中未观察到突变。我们的数据表明，p53突变是频繁的乳腺肿瘤与预后不良，包括高级别或粉刺组织型。有证据表明，p53基因的改变发生在乳腺癌发生的早期，不仅在原位癌，而且在非典型导管增生中检测到突变。
Mutations of the p53 gene appear to be one of the most common abnormalities in human cancer. Although many studies have been published about p53 alterations in breast cancer, data on molecular biological detection of p53 mutations in in situ lesions are still rare, and the implications for breast cancerogenesis are unclear. Tissue samples from 83 patients with different stages of breast cancer and from 13 patients with benign breast lesions were screened for p53 gene mutations by polymerase chain reaction (PCR) followed by temperature-gradient gel electrophoresis (TGGE). p53 protein accumulation was analysed by immunohistochemistry (IHC). Samples were gained from fresh-frozen tissue, scrapings. or paraffin embedded tissue. Additionally, 23 pairs of primary tumours and corresponding lymph nodes were examined. p53 gene aberrations were found in 55.7% of the infiltrating carcinomas, in 31.5% of the ductal carcinomas in situ (DCIS) and in one atypical ductal hyperplasia. A positive correlation was seen with high-grade tumours and with comedo. There was no statistically significant relationship with respect to age, menopausal status, tumour size, hormone receptor status or lymphatic invasion. Concordance between TGGE and IHC was seen in only 63% of the cases analysed. However, with regard to p53 mutation screening by TGGE, a high significance (P = 0.0008) was seen between standard tissue extraction and our scrape preparation technique. Among 8 pairs of primary tumours and their corresponding lymph node metastases, only 3 harbored identical p53 mutations in the same exon, while in 5 cases with mutant p53 in the primaries, no mutation was seen in the lymph node. Our data indicate that p53 mutations are frequent in breast tumours associated with unfavorable prognosis, including high-grade or the comedo histotype. There is evidence that p53 gene alterations occur early in breast cancerogenesis, as mutations were detected not only in in situ carcinomas but also in atypical ductal hyperplasia.