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[Cancer Research 59, 3251-3256, July 1, 1999]
© 1999 American Association for Cancer Research

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[Cancer Research 59, 3251-3256, July 1, 1999]
© 1999 American Association for Cancer Research


Tumor Biology

Presence of Tumor DNA in Plasma of Breast Cancer Patients

Clinicopathological Correlations1

Jose M. Silva, Gemma Dominguez, Jose M. Garcia, Rocio Gonzalez, Maria J. Villanueva, Fatima Navarro, Mariano Provencio, Santiago San Martin, Pilar España and Felix Bonilla2

Department of Medical Oncology, Clinica Puerta de Hierro [J. M. S., G. D., J. M. G., R. G., M. J. V., F. N., M. P., P. E., F. B.], and Department of Gynecology, Hospital Santa Cristina [S. S. M.], 28035 Madrid, Spain

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 III, 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.




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