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在人类乳腺癌中,黏着斑激酶(FAK)过表达与p53突变高度相关。

FAK overexpression and p53 mutations are highly correlated in human breast cancer.

作者信息

Golubovskaya Vita M, Conway-Dorsey Kathleen, Edmiston Sharon N, Tse Chiu-Kit, Lark Amy A, Livasy Chad A, Moore Dominic, Millikan Robert C, Cance William G

机构信息

Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.

出版信息

Int J Cancer. 2009 Oct 1;125(7):1735-8. doi: 10.1002/ijc.24486.

Abstract

Focal adhesion kinase (FAK) is overexpressed in a number of tumors, including breast cancer. Another marker of breast cancer tumorigenesis is the tumor suppressor gene p53 that is frequently mutated in breast cancer. In the present study, our aim was to find a correlation between FAK overexpression, p53 expression and mutation status in a population-based series of invasive breast cancer tumors from the Carolina Breast Cancer Study. Immunohistochemical analyses of 622 breast cancer tumors revealed that expression of FAK and p53 were highly correlated (p = 0.0002) and FAK positive tumors were 1.8 times more likely to be p53 positive compared to FAK negative tumors [odds ratio (OR) = 1.8; 95% Confidence Interval (CI) 1.2-2.8, adjusted for age, race and stage at diagnosis]. Tumors positive for p53 expression showed higher intensity of FAK staining (p < 0.0001) and higher percent of FAK positive staining (p < 0.0005). From the same study, we evaluated 596 breast tumors for mutations in the p53 gene, using single strand conformational polymorphism and sequencing. Statistical analyses were performed to determine the correlation between p53 mutation status and FAK expression in these tumors. We found that FAK expression and p53 mutation were positively correlated (p < 0.0001) and FAK positive tumors were 2.5 times more likely to be p53 mutation positive compared to FAK negative tumors [adjusted OR = 2.5, 95% CI 1.6-3.9]. This is the first analysis demonstrating a high correlation between FAK expression and p53 mutations in a population-based series of breast tumors.

摘要

粘着斑激酶(FAK)在包括乳腺癌在内的多种肿瘤中过表达。乳腺癌发生的另一个标志物是肿瘤抑制基因p53,它在乳腺癌中经常发生突变。在本研究中,我们的目的是在卡罗来纳乳腺癌研究中基于人群的一系列浸润性乳腺癌肿瘤中,寻找FAK过表达、p53表达与突变状态之间的相关性。对622例乳腺癌肿瘤进行免疫组织化学分析发现,FAK和p53的表达高度相关(p = 0.0002),与FAK阴性肿瘤相比,FAK阳性肿瘤的p53阳性可能性高1.8倍[比值比(OR)= 1.8;95%置信区间(CI)1.2 - 2.8,根据年龄、种族和诊断时的分期进行调整]。p53表达阳性的肿瘤显示出更高强度的FAK染色(p < 0.0001)和更高百分比的FAK阳性染色(p < 0.0005)。在同一研究中,我们使用单链构象多态性和测序技术评估了596例乳腺肿瘤中p53基因的突变情况。进行统计分析以确定这些肿瘤中p53突变状态与FAK表达之间的相关性。我们发现FAK表达与p53突变呈正相关(p < 0.0001),与FAK阴性肿瘤相比,FAK阳性肿瘤的p53突变阳性可能性高2.5倍[调整后的OR = 2.5,95% CI 1.6 - 3.9]。这是首次在基于人群的一系列乳腺肿瘤中分析证明FAK表达与p53突变之间存在高度相关性。

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