Silva J M, Dominguez G, Garcia J M, Gonzalez R, Villanueva M J, Navarro F, Provencio M, San Martin S, España P, Bonilla F
Department of Medical Oncology, Clinica Puerta de Hierro, Madrid, Spain.
Cancer Res. 1999 Jul 1;59(13):3251-6.
Using different molecular techniques, DNA has been detected in the plasma of cancer patients with various types of tumors. We undertook the present study to investigate the presence of plasma DNA, before mastectomy, in patients with breast cancer at diagnosis and to analyze the clinicopathological spectrum of this subgroup of patients with respect to patients without DNA with tumor characteristics. We studied 62 patients with breast cancer, who were selected sequentially after mastectomy and diagnosis of breast carcinomas. Genomic DNA extracted from tumor and normal tissues, normal blood cells, and plasma was used for molecular studies. Alterations in polymorphic markers selected because they had been found to show a high rate of alterations in breast cancer in previous studies (D17S855, D17S654, D16S421, TH2, D10S197, and D9S161), as well as mutations in the p53 gene and aberrant methylation at the first exon of p16INK4a, were used to identify and characterize tumor and plasma DNA. Thirteen clinicopathological parameters were analyzed in each patient. We identified 56 cases (90%) with at least one molecular event in tumor DNA, and 41 cases (66%) with a similar alteration in plasma DNA. Comparison of the clinicopathological parameters between patients with and without plasma DNA revealed significant differences in the axillary involvement, rate of invasive ductal carcinoma, high proliferative index, and the parameter comprised of lymph node metastases, histological grade II, and peritumoral vessel involvement. A high proportion of breast cancer patients exhibited plasma DNA at diagnosis similar to tumor DNA, and its presence correlated significantly with pathological parameters associated with a poor prognosis.
运用不同的分子技术，已在患有各类肿瘤的癌症患者血浆中检测到DNA。我们开展本研究，旨在调查乳腺癌患者在诊断时、乳房切除术之前血浆DNA的存在情况，并分析该亚组患者与无DNA肿瘤特征患者相比的临床病理特征。我们研究了62例乳腺癌患者，这些患者在乳房切除术后及乳腺癌诊断后依次入选。从肿瘤组织、正常组织、正常血细胞和血浆中提取的基因组DNA用于分子研究。选择多态性标记的改变，因为在先前研究中已发现它们在乳腺癌中显示出高改变率（D17S855、D17S654、D16S421、TH2、D10S197和D9S161），以及p53基因的突变和p16INK4a第一外显子的异常甲基化，用于鉴定和表征肿瘤及血浆DNA。对每位患者分析了13项临床病理参数。我们在肿瘤DNA中鉴定出56例（90%）至少有一个分子事件，在血浆DNA中有41例（66%）有类似改变。有和无血浆DNA患者的临床病理参数比较显示，在腋窝受累、浸润性导管癌发生率、高增殖指数以及由淋巴结转移、组织学II级和肿瘤周围血管受累组成的参数方面存在显著差异。高比例的乳腺癌患者在诊断时血浆DNA与肿瘤DNA相似，其存在与预后不良相关的病理参数显著相关。
